enrique contreras - Academia.edu (original) (raw)

Papers by enrique contreras

Research paper thumbnail of A Data Mining Methodology for Event Analysis in Neurophysiological Signals

Research paper thumbnail of La noticia de Rufino sobre Gregorio Taumaturgo en su traducción de la Historia Eclesiástica de Eusebio de Cesarea

Research paper thumbnail of Calcium channel antagonists and adenosine analogues decrease tolerance to opiate pentazocine and U 50488H

General Pharmacology: The Vascular System, 1993

A single dose of pentazocine induces cross-tolerance the analgesic effects of the kappa agonist U... more A single dose of pentazocine induces cross-tolerance the analgesic effects of the kappa agonist U 50488H. Tolerance is observed by means of the hot plate test or by the i.p. administration of acetic acid 6 or 24 hr after the priming dose, respectively. 2. The administration of the calcium channel antagonists, diltiazem, nifedipine or verapamil, reduces the degree of tolerance as assessed by the hot plate test or acetic acid administration. 3. The adenosine agonist N6-cyclopentyl adenosine significantly reduced the intensity of the process; in contrast, N6-cyclohexyladenosine antagonized the analgesic response to the opiate obscuring its influence on the process. 4. The results are discussed in relation to the interaction of calcium channel function in the analgesic response to the kappa opiates.

Research paper thumbnail of Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized Cat

Frontiers in computational neuroscience, 2017

In a previous study we developed a Machine Learning procedure for the automatic identification an... more In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials (CDPs). This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random) patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure t...

Research paper thumbnail of Further studies on the effects of acamprosate on tolerance to the analgesic effects of morphine and NO synthesis in the brain

Health, 2013

The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme... more The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme responsible for neuronal NO synthesis (nNOS) in the nucleus accumbens (NAc) of mice chronically treated with morphine and during the abstinence syndrome induced by naloxone. The enzyme was monitored by the NADPH diaphorase method. The number of cells stained for NADPH diaphorase in the NAc of mice was counted in 40 µm thick coronal brain slices at 40X. The intensity of the histochemical reaction of stained cells from naive morphine plus saline and morphine plus acamprosate treated mice was analyzed by Image Pro Plus 4.5.1. Morphine administered in a slow release preparation increased the stain intensity of the positive neurons. The increase in the NADPH staining persisted after naloxone was given to mice chronically treated with morphine. Acamprosate antagonized the effects induced by chronic morphine treatment in the NAc of mice. These results indicate that up-regulation of nNOS in the NAc is a consequence of the sustained effects of morphine stimulation, which, in turn, may result from an increased in glutamate release during the abstinence syndrome.

Research paper thumbnail of Effect of Precipitated Withdrawal on Extracellular Glutamate and Aspartate in the Nucleus Accumbens of Chronically Morphine-Treated Rats: An In Vivo Microdialysis Study

Pharmacology Biochemistry and Behavior, 1998

Effect of precipitated withdrawal on extracellular glutamate and aspartate in the nucleus accumbe... more Effect of precipitated withdrawal on extracellular glutamate and aspartate in the nucleus accumbens of chronically morphine-treated rats: An in vivo microdialysis study. PHARMACOL BIOCHEM BEHAV 60 (1) 255-262, 1998.-Excitatory amino acids release during morphine or naloxone administration was studied in rats. Microdialysis in freely moving animals and capillary electrophoresis with laser-induced fluorescence detection were used to measure several amino acids including glutamate and aspartate in the extracellular fluid at the nucleus accumbens. Perfusion with a calcium-free Ringer's solution decreased glutamate and aspartate in nucleus accumbens dialysates to 35% of its baseline levels, suggesting partial synaptic origin of these amino acids. The first morphine injection decreased glutamate and aspartate to 50% of its baseline level. After repeated morphine injections this effect disappeared, suggesting tolerance. Naloxone injections to morphine-dependent rats increased 300% glutamate and aspartate release; these experiments suggest that excitatory amino acid release in the nucleus accumbens might play a role in morphine withdrawal.

Research paper thumbnail of Neurochemical changes of the extracellular concentrations of glutamate and aspartate in the nucleus accumbens of rats after chronic administration of morphine

European Journal of Pharmacology, 2004

The effects of discontinuing a chronic morphine treatment on the concentrations of glutamate and ... more The effects of discontinuing a chronic morphine treatment on the concentrations of glutamate and aspartate were analyzed in the nucleus accumbens of unrestrained unanesthetized rats. The administration of naloxone or the cessation of morphine administration resulted in increased concentrations of glutamate and aspartate in this central nervous system area. These increased amino acid concentrations were observed a few minutes after naloxone administration and persisted in the controls 48 h after the last dose of the opiate. Morphine withdrawal was also studied in rats not injected with naloxone. In these latter animals, increased concentrations of glutamate and aspartate persisted in controls 96 h after the last dose of the opiate. Single doses of morphine, acamprosate or riluzole administered to rats previously withdrawn from chronic morphine treatment restored the amino acid concentrations to normal levels. These results suggest that the maintenance of increased levels of amino acids could be the expression of new adjustments in central nervous system neurotransmission after discontinuation of the chronic morphine treatment.

Research paper thumbnail of Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance

European Journal of Pharmacology, 1988

Research paper thumbnail of Neurochemical changes after morphine, dizocilpine or riluzole in the ventral posterolateral thalamic nuclei of rats with hyperalgesia

European Journal of Pharmacology, 2000

A number of studies suggest the involvement of glutamate in central hyperalgesia through NMDA rec... more A number of studies suggest the involvement of glutamate in central hyperalgesia through NMDA receptors in animal models of inflammation. Most studies analyze glutamate effects at the spinal cord level. In this work, the effects of morphine, dizocilpine and riluzole on the hyperalgesia induced by carrageenan administration in the rat paw model were investigated. The effects of morphine and riluzole on the release of glutamate and aspartate and on the concentrations of citrulline and arginine in dialysates of the ventral posterolateral nucleus of the thalamus were also examined. All three drugs decreased hyperalgesia when administered prior to carrageenan injection. Morphine decreased the glutamate concentration in dialysates of the ventral posterolateral nucleus but did not affect the concentrations of the other amino acids. The effect of morphine was observed in the absence of painful stimulation and when pressure applied to the rat paw induced a nociceptive reaction. Riluzole decreased the concentrations of glutamate and aspartate and those of citrulline and arginine in the presence or absence of painful stimulation. These experiments suggest that morphine and riluzole attenuate the hyperalgesia induced by injection of carrageenan in the rat hind paw, at least partly, by decreasing glutamate release in the ventral posterolateral thalamic nucleus.

Research paper thumbnail of Acamprosate decreases the induction of tolerance and physical dependence in morphine-treated mice

European Journal of Pharmacology, 2002

The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate (NMDA) receptors... more The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate (NMDA) receptors in the central nervous system (CNS), were examined on the antinociceptive action of morphine, induction of tolerance to and physical dependence on morphine, and expression of the abstinence syndrome to the opiate in mice. For the induction of tolerance and dependence, morphine (300 mg/kg) was administered by means of a slow-release preparation. Single doses of acamprosate (50, 100, 200, or 400 mg/kg) administered 30 min before a test dose of morphine did not change the antinociceptive effects of morphine in drug-naive mice. The drug was also administered in repeated doses (50, 100, 200, or 400 mg/kg, 30 min before and 12 and 24 h after the priming dose of morphine) in order to evaluate its effects on the induction of tolerance; all doses assayed, except the 400 mg/kg, did not affect the intensity of tolerance. The acute administration of acamprosate (50, 100, 200, or 400 mg/kg, injected 30 min before naloxone to morphine-pretreated mice) did not affect the intensity of the abstinence behavior. However, the repeated administration of 100 mg/kg of acamprosate (30 min before and 12 and 24 h after the priming dose of morphine) decreased the intensity of physical dependence. The results of these studies suggest that acamprosate may have modulatory effects on glutamatergic neurotransmission participating in the adaptive mechanisms induced by chronic morphine treatment.

Research paper thumbnail of Dizepam induces tolerance in the isolated skin of Pleurodema thaul

European Journal of Pharmacology, 1995

The effects of the long-term administration of diazepam on the potential difference and short-cir... more The effects of the long-term administration of diazepam on the potential difference and short-circuit current of the isolated skin of the toad Pleurodema thaul (P. thaul) were investigated. Diazepam applied in a concentration range of 4.6 × 10-6 to 5.2 × 10-5 M decreased both electrical parameters. This response was unaffected by flumazenil indicating that the action of diazepam is not induced through benzodiazepine receptors. Induction of tolerance to diazepam on its observed effects on potential difference and short-circuit current was obtained by the administration of a single dose of the drug in a slow release preparation. Skins tolerant to diazepam were also tolerant to the acute effects of verapamil on both electric parameters. Tolerance to diazepam effects was partly reversed by increasing Ca 2+ concentration in the inner bathing solution. The results are consistent with a Ca 2+ channel blocking effect of diazepam in the P. thaul skin.

Research paper thumbnail of Riluzole decreases the abstinence syndrome and physical dependence in morphine-dependent mice

European Journal of Pharmacology, 1999

The effects of the antiglutamatergic agent, riluzole, were examined on the antinociceptive action... more The effects of the antiglutamatergic agent, riluzole, were examined on the antinociceptive action of morphine, on the induction of physical dependence, and on the expression of the abstinence syndrome to the opiate in mice. Morphine was administered as a single dose Ž. 200 mgrkg of a slow-release preparation. Acute and chronic administration of riluzole decreased the analgesic response to morphine, Ž. the intensity of abstinence behavior administered 30 min before a dose of naloxone , and the development of physical dependence Ž. repeatedly administered during the period of chronic morphine treatment .

Research paper thumbnail of Possible role of nitric oxide in the antinociceptive action of intraventricular bradykinin in mice

European Journal of Pharmacology, 1996

The i.c.v, administration of bradykinin (4, 8 and 16 ~xg) induced antinociception in mice which w... more The i.c.v, administration of bradykinin (4, 8 and 16 ~xg) induced antinociception in mice which was resistant to naloxone; furthermore, the induction of tolerance to morphine by a single s.c. injection (100 mg/kg, 24 h before test doses of the peptide) did not affect antinociception. Since bradykinin is known to increase nitric oxide (NO) in peripheral tissues, we studied the possibility that its antinociceptive action may be related to NO effects in the central nervous system. Bradykinin effects were antagonized by previous treatment with NG-nitro-L-arginine or concomitant i.c.v, administration of bradykinin and methylene blue. The immediate precursor of NO, L-arginine, which by itself produces analgesia, also reduced bradykinin effects; moreover, tolerance to L-arginine significantly decreased the response to the peptide. These results suggest that NO is involved in antinociception induced by i.c.v, administration of bradykinin.

Research paper thumbnail of Further studies on the effects of acamprosate on tolerance to the analgesic effects of morphine and NO synthesis in the brain

Jacqueline Sepúlveda, Andrea Ortega, Jorge Roa, Enrique Contreras

The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme... more The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme responsible for neuronal NO synthesis (nNOS) in the nucleus accumbens (NAc) of mice chronically treated with morphine and during the abstinence syndrome induced by naloxone. The enzyme was monitored by the NADPH diaphorase method. The number of cells stained for NADPH diaphorase in the NAc of mice was counted in 40 μm thick coronal brain slices at 40X. The intensity of the histochemical reaction of stained cells from naive morphine plus saline and morphine plus acamprosate treated mice was analyzed by Image Pro Plus 4.5.1. Morphine administered in a slow release preparation increased the stain intensity of the positive neurons. The increase in the NADPH staining persisted after naloxone was given to mice chronically treated with morphine. Acamprosate antagonized the effects induced by chronic morphine treatment in the NAc of mice. These results indicate that up-regulation of nNOS in the...

Research paper thumbnail of Bradykinin facilitates the purinergic motor component of the rat bladder neurotransmission

Neuroscience Letters, 1990

Research paper thumbnail of Endogenous Nitric Oxide Attenuates Ethanol-lnduced Vasoconstriction in the Human Placenta

Gynecologic and Obstetric Investigation, 1997

The purpose of this study was to clarify the role of endogenous nitric oxide and prostanoids in e... more The purpose of this study was to clarify the role of endogenous nitric oxide and prostanoids in ethanol-induced perturbation of microcirculation in perfused human placenta. Infusion of ethanol into chorionic plate vessels at 10–65 mM increases perfusion pressure in a concentration-dependent fashion, and is an indicator of fetal-placental vasoconstriction. Simultaneous infusion of Nω-nitro-L-arginine, methylene blue and endothelial cell removal significantly

Research paper thumbnail of Sensitivity of Mouse Vas Deferens to Neurotransmitters: Changes After Morphine Treatment

British Journal of Pharmacology, 1979

1. The pharmacological responses of the isolated vas deferens of the mouse were investigated afte... more 1. The pharmacological responses of the isolated vas deferens of the mouse were investigated after acute and chronic treatment with morphine. 2. The addition of morphine to the bath did not alter the responses of the vas deferens to exogenous noradrenaline, adrenaline or dopamine. 3. Low doses of morphine depressed the responses to acetylcholine. Very high concentrations of the opioid (8.5 x 10(-4) M) completely abolished, in about 50% of the preparations, the responses to exogenous acetylcholine, while in the other 50% a potentiation of the responses to low concentrations of acetylcholine was observed. 4. The vas deferens of mice chronically treated with morphine showed increased sensitivity to exogenous noradrenaline, but decreased sensitivity to acetylcholine. 5. A fresh amount of morphine added to the bath enhanced the responses of morphine-tolerant preparations to noradrenaline but not to dopamine or acetylcholine. The specificity of this phenomenon was demonstrated by the use of pentobarbitone instead of the opioid. 6. These results are in agreement with the theory that tolerance could result from a form of disuse supersensitivity.

Research paper thumbnail of Influence of opiate tolerance and calcium channel antagonists on the antinociceptive effects of L-arginine and NG-nitro L-arginine* 1

… : The Vascular System, 1997

1. 1. The antinociceptive effects induced by L-arginine (L-Arg 300–600 mg sc) or N G -nitro-L-arg... more 1. 1. The antinociceptive effects induced by L-arginine (L-Arg 300–600 mg sc) or N G -nitro-L-arginine (NOArg 20–70 mg sc) in mice were assessed by the hot-plate test. 2. 2. The antinociception induced by both agents was antagonized by naloxone. L-Arg significantly ...

Research paper thumbnail of Acamprosate decreases the induction of tolerance and physical dependence in morphine-treated mice

European Journal of Pharmacology, 2002

The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate (NMDA) receptors... more The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate (NMDA) receptors in the central nervous system (CNS), were examined on the antinociceptive action of morphine, induction of tolerance to and physical dependence on morphine, and expression of the abstinence syndrome to the opiate in mice. For the induction of tolerance and dependence, morphine (300 mg/kg) was administered by means of a slow-release preparation. Single doses of acamprosate (50, 100, 200, or 400 mg/kg) administered 30 min before a test dose of morphine did not change the antinociceptive effects of morphine in drug-naive mice. The drug was also administered in repeated doses (50, 100, 200, or 400 mg/kg, 30 min before and 12 and 24 h after the priming dose of morphine) in order to evaluate its effects on the induction of tolerance; all doses assayed, except the 400 mg/kg, did not affect the intensity of tolerance. The acute administration of acamprosate (50, 100, 200, or 400 mg/kg, injected...

Research paper thumbnail of Dizepam induces tolerance in the isolated skin of Pleurodema thaul

European Journal of Pharmacology, 1995

The effects of the long-term administration of diazepam on the potential difference and short-cir... more The effects of the long-term administration of diazepam on the potential difference and short-circuit current of the isolated skin of the toad Pleurodema thaul (P. thaul) were investigated. Diazepam applied in a concentration range of 4.6 × 10-6 to 5.2 × 10-5 M decreased both electrical parameters. This response was unaffected by flumazenil indicating that the action of diazepam is not induced through benzodiazepine receptors. Induction of tolerance to diazepam on its observed effects on potential difference and short-circuit current was obtained by the administration of a single dose of the drug in a slow release preparation. Skins tolerant to diazepam were also tolerant to the acute effects of verapamil on both electric parameters. Tolerance to diazepam effects was partly reversed by increasing Ca 2+ concentration in the inner bathing solution. The results are consistent with a Ca 2+ channel blocking effect of diazepam in the P. thaul skin.

Research paper thumbnail of A Data Mining Methodology for Event Analysis in Neurophysiological Signals

Research paper thumbnail of La noticia de Rufino sobre Gregorio Taumaturgo en su traducción de la Historia Eclesiástica de Eusebio de Cesarea

Research paper thumbnail of Calcium channel antagonists and adenosine analogues decrease tolerance to opiate pentazocine and U 50488H

General Pharmacology: The Vascular System, 1993

A single dose of pentazocine induces cross-tolerance the analgesic effects of the kappa agonist U... more A single dose of pentazocine induces cross-tolerance the analgesic effects of the kappa agonist U 50488H. Tolerance is observed by means of the hot plate test or by the i.p. administration of acetic acid 6 or 24 hr after the priming dose, respectively. 2. The administration of the calcium channel antagonists, diltiazem, nifedipine or verapamil, reduces the degree of tolerance as assessed by the hot plate test or acetic acid administration. 3. The adenosine agonist N6-cyclopentyl adenosine significantly reduced the intensity of the process; in contrast, N6-cyclohexyladenosine antagonized the analgesic response to the opiate obscuring its influence on the process. 4. The results are discussed in relation to the interaction of calcium channel function in the analgesic response to the kappa opiates.

Research paper thumbnail of Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized Cat

Frontiers in computational neuroscience, 2017

In a previous study we developed a Machine Learning procedure for the automatic identification an... more In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials (CDPs). This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random) patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure t...

Research paper thumbnail of Further studies on the effects of acamprosate on tolerance to the analgesic effects of morphine and NO synthesis in the brain

Health, 2013

The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme... more The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme responsible for neuronal NO synthesis (nNOS) in the nucleus accumbens (NAc) of mice chronically treated with morphine and during the abstinence syndrome induced by naloxone. The enzyme was monitored by the NADPH diaphorase method. The number of cells stained for NADPH diaphorase in the NAc of mice was counted in 40 µm thick coronal brain slices at 40X. The intensity of the histochemical reaction of stained cells from naive morphine plus saline and morphine plus acamprosate treated mice was analyzed by Image Pro Plus 4.5.1. Morphine administered in a slow release preparation increased the stain intensity of the positive neurons. The increase in the NADPH staining persisted after naloxone was given to mice chronically treated with morphine. Acamprosate antagonized the effects induced by chronic morphine treatment in the NAc of mice. These results indicate that up-regulation of nNOS in the NAc is a consequence of the sustained effects of morphine stimulation, which, in turn, may result from an increased in glutamate release during the abstinence syndrome.

Research paper thumbnail of Effect of Precipitated Withdrawal on Extracellular Glutamate and Aspartate in the Nucleus Accumbens of Chronically Morphine-Treated Rats: An In Vivo Microdialysis Study

Pharmacology Biochemistry and Behavior, 1998

Effect of precipitated withdrawal on extracellular glutamate and aspartate in the nucleus accumbe... more Effect of precipitated withdrawal on extracellular glutamate and aspartate in the nucleus accumbens of chronically morphine-treated rats: An in vivo microdialysis study. PHARMACOL BIOCHEM BEHAV 60 (1) 255-262, 1998.-Excitatory amino acids release during morphine or naloxone administration was studied in rats. Microdialysis in freely moving animals and capillary electrophoresis with laser-induced fluorescence detection were used to measure several amino acids including glutamate and aspartate in the extracellular fluid at the nucleus accumbens. Perfusion with a calcium-free Ringer's solution decreased glutamate and aspartate in nucleus accumbens dialysates to 35% of its baseline levels, suggesting partial synaptic origin of these amino acids. The first morphine injection decreased glutamate and aspartate to 50% of its baseline level. After repeated morphine injections this effect disappeared, suggesting tolerance. Naloxone injections to morphine-dependent rats increased 300% glutamate and aspartate release; these experiments suggest that excitatory amino acid release in the nucleus accumbens might play a role in morphine withdrawal.

Research paper thumbnail of Neurochemical changes of the extracellular concentrations of glutamate and aspartate in the nucleus accumbens of rats after chronic administration of morphine

European Journal of Pharmacology, 2004

The effects of discontinuing a chronic morphine treatment on the concentrations of glutamate and ... more The effects of discontinuing a chronic morphine treatment on the concentrations of glutamate and aspartate were analyzed in the nucleus accumbens of unrestrained unanesthetized rats. The administration of naloxone or the cessation of morphine administration resulted in increased concentrations of glutamate and aspartate in this central nervous system area. These increased amino acid concentrations were observed a few minutes after naloxone administration and persisted in the controls 48 h after the last dose of the opiate. Morphine withdrawal was also studied in rats not injected with naloxone. In these latter animals, increased concentrations of glutamate and aspartate persisted in controls 96 h after the last dose of the opiate. Single doses of morphine, acamprosate or riluzole administered to rats previously withdrawn from chronic morphine treatment restored the amino acid concentrations to normal levels. These results suggest that the maintenance of increased levels of amino acids could be the expression of new adjustments in central nervous system neurotransmission after discontinuation of the chronic morphine treatment.

Research paper thumbnail of Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance

European Journal of Pharmacology, 1988

Research paper thumbnail of Neurochemical changes after morphine, dizocilpine or riluzole in the ventral posterolateral thalamic nuclei of rats with hyperalgesia

European Journal of Pharmacology, 2000

A number of studies suggest the involvement of glutamate in central hyperalgesia through NMDA rec... more A number of studies suggest the involvement of glutamate in central hyperalgesia through NMDA receptors in animal models of inflammation. Most studies analyze glutamate effects at the spinal cord level. In this work, the effects of morphine, dizocilpine and riluzole on the hyperalgesia induced by carrageenan administration in the rat paw model were investigated. The effects of morphine and riluzole on the release of glutamate and aspartate and on the concentrations of citrulline and arginine in dialysates of the ventral posterolateral nucleus of the thalamus were also examined. All three drugs decreased hyperalgesia when administered prior to carrageenan injection. Morphine decreased the glutamate concentration in dialysates of the ventral posterolateral nucleus but did not affect the concentrations of the other amino acids. The effect of morphine was observed in the absence of painful stimulation and when pressure applied to the rat paw induced a nociceptive reaction. Riluzole decreased the concentrations of glutamate and aspartate and those of citrulline and arginine in the presence or absence of painful stimulation. These experiments suggest that morphine and riluzole attenuate the hyperalgesia induced by injection of carrageenan in the rat hind paw, at least partly, by decreasing glutamate release in the ventral posterolateral thalamic nucleus.

Research paper thumbnail of Acamprosate decreases the induction of tolerance and physical dependence in morphine-treated mice

European Journal of Pharmacology, 2002

The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate (NMDA) receptors... more The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate (NMDA) receptors in the central nervous system (CNS), were examined on the antinociceptive action of morphine, induction of tolerance to and physical dependence on morphine, and expression of the abstinence syndrome to the opiate in mice. For the induction of tolerance and dependence, morphine (300 mg/kg) was administered by means of a slow-release preparation. Single doses of acamprosate (50, 100, 200, or 400 mg/kg) administered 30 min before a test dose of morphine did not change the antinociceptive effects of morphine in drug-naive mice. The drug was also administered in repeated doses (50, 100, 200, or 400 mg/kg, 30 min before and 12 and 24 h after the priming dose of morphine) in order to evaluate its effects on the induction of tolerance; all doses assayed, except the 400 mg/kg, did not affect the intensity of tolerance. The acute administration of acamprosate (50, 100, 200, or 400 mg/kg, injected 30 min before naloxone to morphine-pretreated mice) did not affect the intensity of the abstinence behavior. However, the repeated administration of 100 mg/kg of acamprosate (30 min before and 12 and 24 h after the priming dose of morphine) decreased the intensity of physical dependence. The results of these studies suggest that acamprosate may have modulatory effects on glutamatergic neurotransmission participating in the adaptive mechanisms induced by chronic morphine treatment.

Research paper thumbnail of Dizepam induces tolerance in the isolated skin of Pleurodema thaul

European Journal of Pharmacology, 1995

The effects of the long-term administration of diazepam on the potential difference and short-cir... more The effects of the long-term administration of diazepam on the potential difference and short-circuit current of the isolated skin of the toad Pleurodema thaul (P. thaul) were investigated. Diazepam applied in a concentration range of 4.6 × 10-6 to 5.2 × 10-5 M decreased both electrical parameters. This response was unaffected by flumazenil indicating that the action of diazepam is not induced through benzodiazepine receptors. Induction of tolerance to diazepam on its observed effects on potential difference and short-circuit current was obtained by the administration of a single dose of the drug in a slow release preparation. Skins tolerant to diazepam were also tolerant to the acute effects of verapamil on both electric parameters. Tolerance to diazepam effects was partly reversed by increasing Ca 2+ concentration in the inner bathing solution. The results are consistent with a Ca 2+ channel blocking effect of diazepam in the P. thaul skin.

Research paper thumbnail of Riluzole decreases the abstinence syndrome and physical dependence in morphine-dependent mice

European Journal of Pharmacology, 1999

The effects of the antiglutamatergic agent, riluzole, were examined on the antinociceptive action... more The effects of the antiglutamatergic agent, riluzole, were examined on the antinociceptive action of morphine, on the induction of physical dependence, and on the expression of the abstinence syndrome to the opiate in mice. Morphine was administered as a single dose Ž. 200 mgrkg of a slow-release preparation. Acute and chronic administration of riluzole decreased the analgesic response to morphine, Ž. the intensity of abstinence behavior administered 30 min before a dose of naloxone , and the development of physical dependence Ž. repeatedly administered during the period of chronic morphine treatment .

Research paper thumbnail of Possible role of nitric oxide in the antinociceptive action of intraventricular bradykinin in mice

European Journal of Pharmacology, 1996

The i.c.v, administration of bradykinin (4, 8 and 16 ~xg) induced antinociception in mice which w... more The i.c.v, administration of bradykinin (4, 8 and 16 ~xg) induced antinociception in mice which was resistant to naloxone; furthermore, the induction of tolerance to morphine by a single s.c. injection (100 mg/kg, 24 h before test doses of the peptide) did not affect antinociception. Since bradykinin is known to increase nitric oxide (NO) in peripheral tissues, we studied the possibility that its antinociceptive action may be related to NO effects in the central nervous system. Bradykinin effects were antagonized by previous treatment with NG-nitro-L-arginine or concomitant i.c.v, administration of bradykinin and methylene blue. The immediate precursor of NO, L-arginine, which by itself produces analgesia, also reduced bradykinin effects; moreover, tolerance to L-arginine significantly decreased the response to the peptide. These results suggest that NO is involved in antinociception induced by i.c.v, administration of bradykinin.

Research paper thumbnail of Further studies on the effects of acamprosate on tolerance to the analgesic effects of morphine and NO synthesis in the brain

Jacqueline Sepúlveda, Andrea Ortega, Jorge Roa, Enrique Contreras

The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme... more The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme responsible for neuronal NO synthesis (nNOS) in the nucleus accumbens (NAc) of mice chronically treated with morphine and during the abstinence syndrome induced by naloxone. The enzyme was monitored by the NADPH diaphorase method. The number of cells stained for NADPH diaphorase in the NAc of mice was counted in 40 μm thick coronal brain slices at 40X. The intensity of the histochemical reaction of stained cells from naive morphine plus saline and morphine plus acamprosate treated mice was analyzed by Image Pro Plus 4.5.1. Morphine administered in a slow release preparation increased the stain intensity of the positive neurons. The increase in the NADPH staining persisted after naloxone was given to mice chronically treated with morphine. Acamprosate antagonized the effects induced by chronic morphine treatment in the NAc of mice. These results indicate that up-regulation of nNOS in the...

Research paper thumbnail of Bradykinin facilitates the purinergic motor component of the rat bladder neurotransmission

Neuroscience Letters, 1990

Research paper thumbnail of Endogenous Nitric Oxide Attenuates Ethanol-lnduced Vasoconstriction in the Human Placenta

Gynecologic and Obstetric Investigation, 1997

The purpose of this study was to clarify the role of endogenous nitric oxide and prostanoids in e... more The purpose of this study was to clarify the role of endogenous nitric oxide and prostanoids in ethanol-induced perturbation of microcirculation in perfused human placenta. Infusion of ethanol into chorionic plate vessels at 10–65 mM increases perfusion pressure in a concentration-dependent fashion, and is an indicator of fetal-placental vasoconstriction. Simultaneous infusion of Nω-nitro-L-arginine, methylene blue and endothelial cell removal significantly

Research paper thumbnail of Sensitivity of Mouse Vas Deferens to Neurotransmitters: Changes After Morphine Treatment

British Journal of Pharmacology, 1979

1. The pharmacological responses of the isolated vas deferens of the mouse were investigated afte... more 1. The pharmacological responses of the isolated vas deferens of the mouse were investigated after acute and chronic treatment with morphine. 2. The addition of morphine to the bath did not alter the responses of the vas deferens to exogenous noradrenaline, adrenaline or dopamine. 3. Low doses of morphine depressed the responses to acetylcholine. Very high concentrations of the opioid (8.5 x 10(-4) M) completely abolished, in about 50% of the preparations, the responses to exogenous acetylcholine, while in the other 50% a potentiation of the responses to low concentrations of acetylcholine was observed. 4. The vas deferens of mice chronically treated with morphine showed increased sensitivity to exogenous noradrenaline, but decreased sensitivity to acetylcholine. 5. A fresh amount of morphine added to the bath enhanced the responses of morphine-tolerant preparations to noradrenaline but not to dopamine or acetylcholine. The specificity of this phenomenon was demonstrated by the use of pentobarbitone instead of the opioid. 6. These results are in agreement with the theory that tolerance could result from a form of disuse supersensitivity.

Research paper thumbnail of Influence of opiate tolerance and calcium channel antagonists on the antinociceptive effects of L-arginine and NG-nitro L-arginine* 1

… : The Vascular System, 1997

1. 1. The antinociceptive effects induced by L-arginine (L-Arg 300–600 mg sc) or N G -nitro-L-arg... more 1. 1. The antinociceptive effects induced by L-arginine (L-Arg 300–600 mg sc) or N G -nitro-L-arginine (NOArg 20–70 mg sc) in mice were assessed by the hot-plate test. 2. 2. The antinociception induced by both agents was antagonized by naloxone. L-Arg significantly ...

Research paper thumbnail of Acamprosate decreases the induction of tolerance and physical dependence in morphine-treated mice

European Journal of Pharmacology, 2002

The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate (NMDA) receptors... more The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate (NMDA) receptors in the central nervous system (CNS), were examined on the antinociceptive action of morphine, induction of tolerance to and physical dependence on morphine, and expression of the abstinence syndrome to the opiate in mice. For the induction of tolerance and dependence, morphine (300 mg/kg) was administered by means of a slow-release preparation. Single doses of acamprosate (50, 100, 200, or 400 mg/kg) administered 30 min before a test dose of morphine did not change the antinociceptive effects of morphine in drug-naive mice. The drug was also administered in repeated doses (50, 100, 200, or 400 mg/kg, 30 min before and 12 and 24 h after the priming dose of morphine) in order to evaluate its effects on the induction of tolerance; all doses assayed, except the 400 mg/kg, did not affect the intensity of tolerance. The acute administration of acamprosate (50, 100, 200, or 400 mg/kg, injected...

Research paper thumbnail of Dizepam induces tolerance in the isolated skin of Pleurodema thaul

European Journal of Pharmacology, 1995

The effects of the long-term administration of diazepam on the potential difference and short-cir... more The effects of the long-term administration of diazepam on the potential difference and short-circuit current of the isolated skin of the toad Pleurodema thaul (P. thaul) were investigated. Diazepam applied in a concentration range of 4.6 × 10-6 to 5.2 × 10-5 M decreased both electrical parameters. This response was unaffected by flumazenil indicating that the action of diazepam is not induced through benzodiazepine receptors. Induction of tolerance to diazepam on its observed effects on potential difference and short-circuit current was obtained by the administration of a single dose of the drug in a slow release preparation. Skins tolerant to diazepam were also tolerant to the acute effects of verapamil on both electric parameters. Tolerance to diazepam effects was partly reversed by increasing Ca 2+ concentration in the inner bathing solution. The results are consistent with a Ca 2+ channel blocking effect of diazepam in the P. thaul skin.