Sabina Fraioli - Academia.edu (original) (raw)
Papers by Sabina Fraioli
Psychopharmacology, 2000
We have previously shown that environmental novelty enhances the behavioral activating effects of... more We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1-3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
Pharmacology Biochemistry and Behavior, 1994
In a study designed to determine whether environmental and pharmacological stimuli have the abili... more In a study designed to determine whether environmental and pharmacological stimuli have the ability to take control of amphetamine-mediated hyperdipsia, rats were injected with d,l-amphetamine (AMPH; 4 mg/kg, IP) alone or in combination with (-)-norpseudoephedrine (NPE; 10 mg/kg, IP) and then returned to the home cage or transferred to a distinct environment (test cage). Water intake was measured hourly for 3 h, in the absence of food. AMPH treatment lasted for 10 days, followed by a 6-day extinction phase during which AMPH, but not NPE, injections were discontinued. Subsequently, all animals received challenge injections: NPE (10 mg/kg) on day 17; AMPH (4 mg/kg) on day 19; and morphine (MOR; 1 mg/kg) on day 21. AMPH-mediated hyperdipsia developed in 50% of animals and had an early onset in the home cage. NPE prevented the AMPH effects. Discontinuation of AMPH treatment promptly normalized drinking in the home cage but increased it further in the test cage. Within 6 days of AMPH discontinuation, hyperdipsia completely disappeared. It was reinstated, in the test cage alone, by a challenge injection of NPE or MOR. We suggest that hyperdipsia is a primary AMPH effect, which in some way is counter-acted by a distinct environment. This appears to elicit a compensatory mechanism that is revealed in the absence of AMPH and is reinstated in a nonspecific way by pharmacological stimuli.
Pharmacology Biochemistry and Behavior, 1996
-(-)-Norpseudoephedrine (NPE), the enantiomer of cathine and a structural analog of phenylpropano... more -(-)-Norpseudoephedrine (NPE), the enantiomer of cathine and a structural analog of phenylpropanolamine, shows anorectic and antidipsic effects that have been referred to its structural analogies with amphetamine. When amphetamine is chronically administered to rats, its anorectic effects fade out, water intake is progressively increased, and the diuretic response to the drug remains stable. Our previous studies show that chronic administration of NPE does not produce the typical amphetamine hyperdipsic response. In the present study, designed to obtain a more detailed picture of the ingestive and diuretic effects of chronic exposure to NPE, we evaluated the effects of 11 daily administrations of three doses of NPE (17, 32, and 56 mg/kg IP) on food and water intake, as well as on diuresis, in rats maintained in conditions of free access to food and water. Results show that all three doses inhibited food intake at 2 h, whereas only the highest dose inhibited food intake at 5 h. No differences between groups were detected at 24 h. These responses remained unchanged throughout the 11 days of treatment, and substitution of NPE with a solvent injection caused no rebound feeding. NPE treatment did not modify the ingestive response to a challenge injection of amphetamine, 0.56 and 1.0 mg/kg IP, given 1 day apart. Although NPE inhibited water intake throughout the experiment, it did so significantly only during the first 2 h postinjection. Urine output in the NPE-treated groups increased significantly on the first day only. These findings make it unlikely that the anorectic effects of NPE depend on an amphetamine-like mechanism of action. In addition, the short-lasting anorectic and antidipsic effects of NPE and the lack of tolerance to them raise the possibility of a therapeutic use of this drug as an adjuvant in the therapy of eating disorders characterized by binge episodes.
Pharmacology Biochemistry and Behavior, 2000
FRAIOLI, S., L. ANTONILLI AND P. NENCINI. Stereoselective morphine-like discriminative properties... more FRAIOLI, S., L. ANTONILLI AND P. NENCINI. Stereoselective morphine-like discriminative properties of a new alkylaminonaphthalenic derivative. PHARMACOL BIOCHEM BEHAV 66 (1) 199-204, 2000.-The morphine-like properties of a series of aminoalkyl-and cycloalkylamino-naphtalenic derivatives of 17-methyl-17-azaequilenine were studied in rats trained to discriminate morphine (5.6 mg/kg IP) from vehicle in a two-lever operant behavioral procedure reinforced by water access. It was found that one of the compounds tested (i.e., A8; 1-ethyl-1-hydroxy-1-[2-(6-hydroxynaphthyl)]-2-methyl-3dimethylaminopropane) fully generalized for the morphine stimulus. The discriminative effects of A8 were stereospecific, as indicated by the fact that ( ϩ )-(1R,2R)-A8 was three times more potent than the racemic compound and that the ( Ϫ )-(1S,2S) enantiomer was completely inactive. ( ϩ )-(1R,2R)-A8 generalization for the morphine cue was inhibited by naloxone. None of the other five derivatives examined generalized for the morphine stimulus. In conclusion, the naphthalenic structure is a source of compounds with stereospecific and naloxone-reversible morphine-like properties.
Neuropsychopharmacology, 1999
We have previously reported that intravenous (I.V.) administrations of 0.5-1.0 mg/kg of amphetami... more We have previously reported that intravenous (I.V.) administrations of 0.5-1.0 mg/kg of amphetamine in the absence of any environmental stimuli predictive of drug administration failed to induce psychomotor sensitization whereas the same drug did produce robust sensitization when given in association with environmental novelty. These results were obtained by studying rotational behavior in animals with a unilateral 6-OHDA lesion of the mesostriatal dopamine system. The purpose of this study was to determine if environmental novelty has a similar effect on sensitization to the locomotor activating effects of amphetamine in neurologically intact rats. Rats were implanted with I.V. catheters and divided in four groups. Two groups were housed in locomotor activity cages and given seven consecutive I.V. infusions of either saline (SAL-HOME group) or 0.375 mg/kg of amphetamine (AMPH-HOME group), using a remotely activated delivery system. Simultaneously, the other two groups were transported to the test cages and given the same treatment (SAL-NOVEL and AMPH-NOVEL groups). After one week withdrawal, all groups were given an amphetamine challenge (0.375 mg/kg, I.V.). Amphetamine sensitization developed when the drug was administered under NOVEL conditions, as indicated by a progressive increase in ampheatmine-induced locomotor activity over test sessions and by a greater response to the amphetamine challenge in the AMPH-pretreated versus the SAL-pretreated group. In contrast, no sensitization was observed under HOME conditions. Similar results were obtained with the analysis of vertical activity. [ Neuropsychopharmacology 20: 533-541, 1999] © 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
Behavioural Brain Research, 1997
The hypothesis that the combined activation of D1 and D2 dopaminergic receptors is instrumental i... more The hypothesis that the combined activation of D1 and D2 dopaminergic receptors is instrumental in inducing amphetamine (AMPH)-mediated hyperdipsia was tested in rats. The D1 agonist SKF-38393 (SKF) and the D2 agonist quinpirole (QNP) were i.p. injected, alone or in combination, to male rats for 10 days. After 2 days of wash-out, a single dose of AMPH (3 mg/kg) was administered. Intake of water and food and diuresis were daily measured at 2, 5 and 24 h. In two further experiments the higher dose of QNP (0.56 mg/kg) was given with two different doses of the D1 antagonist SCH-23390 (SCH), or, respectively, of the peripheral D2 antagonist domperidone (DMP). In a fourth experiment, the possibility that QNP, given alone or in combination with SKF, produces an AMPH-like internal state was evaluated by using a drug-discrimination paradigm. Results show that chronic administration of QNP produced a significant increase of 24 h water intake that was reinstated by AMPH. This QNP effect was only partially prevented by DMP, suggesting a main central mechanism of action. By itself D1 receptor manipulation did not affect water intake, but influenced QNP polydipsia that, accordingly, was enhanced by the lower dose of SKF (0.3 mg/kg) and inhibited by the lower dose of SCH (0.01 mg/kg). In rats trained to discriminate AMPH from solvent, QNP partially generalized for the AMPH stimulus, an effect that was potentiated by SKF. In conclusion, a D1-modulated sensitization of D2 dopaminergic mechanisms is probably involved in AMPH-induced hyperdipsia.
Behavioural Brain Research, 1998
Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances... more Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances the analgesic effects of morphine (MOR). Thus, it is possible that full psychomotor stimulant potency is not required to increase the analgesic action of opiates. The validity of this assumption is here tested by studying the ability of (-)-norpseudoephedrine (NPE), an enantiomer of phenylpropanolamine and a metabolite of cathinone, to influence both the analgesic effects of MOR and its discriminative stimulus properties. In mice NPE (5.6-10.0-17.0 mg/kg i.p.) did not prolong the latency to lick or to remove paws from a plate warmed at 54 degrees C. However, it significantly potentiated the analgesic effect of 3.2 mg/kg of MOR. These results were replicated in rats by use of the formalin test, which measures the numbers of hind paw flinches produced by injecting 50 microl of formalin into the dorsal surface of the paw. The higher dose of NPE (17 mg/kg) increased the effect of sub-analgesic doses of MOR (0.56 and 1.0 mg/kg). In rats trained to discriminate between 0.5 mg/kg of amphetamine and solvent in a two-lever operant behavior reinforced by water access. NPE induced a dose-dependent increment of drug lever responding from 0% at 1.0 mg/kg to 100% at 32.0 mg/kg. In contrast, NPE did not generalize for the MOR cue up to the dose of 56.0 mg/kg, which produced a substantial reduction of the response rate. However, when given in combination, NPE attenuated the discriminative effects of MOR and potentiated its inhibitory action on the response rate. These results exclude a direct action of NPE on the mu opiate system. In conclusion, NPE preserves amphetamine-like properties and these properties are probably responsible for the interaction of the drug with the analgesic and discriminative effects of MOR. Therefore, this study contradicts the assumption that the analgesic effects of MOR can be enhanced by a sympathomimetic drug that lacks significant psychostimulant actions.
Psychopharmacology, 2000
We have previously shown that environmental novelty enhances the behavioral activating effects of... more We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1-3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
Pharmacology Biochemistry and Behavior, 1994
In a study designed to determine whether environmental and pharmacological stimuli have the abili... more In a study designed to determine whether environmental and pharmacological stimuli have the ability to take control of amphetamine-mediated hyperdipsia, rats were injected with d,l-amphetamine (AMPH; 4 mg/kg, IP) alone or in combination with (-)-norpseudoephedrine (NPE; 10 mg/kg, IP) and then returned to the home cage or transferred to a distinct environment (test cage). Water intake was measured hourly for 3 h, in the absence of food. AMPH treatment lasted for 10 days, followed by a 6-day extinction phase during which AMPH, but not NPE, injections were discontinued. Subsequently, all animals received challenge injections: NPE (10 mg/kg) on day 17; AMPH (4 mg/kg) on day 19; and morphine (MOR; 1 mg/kg) on day 21. AMPH-mediated hyperdipsia developed in 50% of animals and had an early onset in the home cage. NPE prevented the AMPH effects. Discontinuation of AMPH treatment promptly normalized drinking in the home cage but increased it further in the test cage. Within 6 days of AMPH discontinuation, hyperdipsia completely disappeared. It was reinstated, in the test cage alone, by a challenge injection of NPE or MOR. We suggest that hyperdipsia is a primary AMPH effect, which in some way is counter-acted by a distinct environment. This appears to elicit a compensatory mechanism that is revealed in the absence of AMPH and is reinstated in a nonspecific way by pharmacological stimuli.
Pharmacology Biochemistry and Behavior, 1996
-(-)-Norpseudoephedrine (NPE), the enantiomer of cathine and a structural analog of phenylpropano... more -(-)-Norpseudoephedrine (NPE), the enantiomer of cathine and a structural analog of phenylpropanolamine, shows anorectic and antidipsic effects that have been referred to its structural analogies with amphetamine. When amphetamine is chronically administered to rats, its anorectic effects fade out, water intake is progressively increased, and the diuretic response to the drug remains stable. Our previous studies show that chronic administration of NPE does not produce the typical amphetamine hyperdipsic response. In the present study, designed to obtain a more detailed picture of the ingestive and diuretic effects of chronic exposure to NPE, we evaluated the effects of 11 daily administrations of three doses of NPE (17, 32, and 56 mg/kg IP) on food and water intake, as well as on diuresis, in rats maintained in conditions of free access to food and water. Results show that all three doses inhibited food intake at 2 h, whereas only the highest dose inhibited food intake at 5 h. No differences between groups were detected at 24 h. These responses remained unchanged throughout the 11 days of treatment, and substitution of NPE with a solvent injection caused no rebound feeding. NPE treatment did not modify the ingestive response to a challenge injection of amphetamine, 0.56 and 1.0 mg/kg IP, given 1 day apart. Although NPE inhibited water intake throughout the experiment, it did so significantly only during the first 2 h postinjection. Urine output in the NPE-treated groups increased significantly on the first day only. These findings make it unlikely that the anorectic effects of NPE depend on an amphetamine-like mechanism of action. In addition, the short-lasting anorectic and antidipsic effects of NPE and the lack of tolerance to them raise the possibility of a therapeutic use of this drug as an adjuvant in the therapy of eating disorders characterized by binge episodes.
Pharmacology Biochemistry and Behavior, 2000
FRAIOLI, S., L. ANTONILLI AND P. NENCINI. Stereoselective morphine-like discriminative properties... more FRAIOLI, S., L. ANTONILLI AND P. NENCINI. Stereoselective morphine-like discriminative properties of a new alkylaminonaphthalenic derivative. PHARMACOL BIOCHEM BEHAV 66 (1) 199-204, 2000.-The morphine-like properties of a series of aminoalkyl-and cycloalkylamino-naphtalenic derivatives of 17-methyl-17-azaequilenine were studied in rats trained to discriminate morphine (5.6 mg/kg IP) from vehicle in a two-lever operant behavioral procedure reinforced by water access. It was found that one of the compounds tested (i.e., A8; 1-ethyl-1-hydroxy-1-[2-(6-hydroxynaphthyl)]-2-methyl-3dimethylaminopropane) fully generalized for the morphine stimulus. The discriminative effects of A8 were stereospecific, as indicated by the fact that ( ϩ )-(1R,2R)-A8 was three times more potent than the racemic compound and that the ( Ϫ )-(1S,2S) enantiomer was completely inactive. ( ϩ )-(1R,2R)-A8 generalization for the morphine cue was inhibited by naloxone. None of the other five derivatives examined generalized for the morphine stimulus. In conclusion, the naphthalenic structure is a source of compounds with stereospecific and naloxone-reversible morphine-like properties.
Neuropsychopharmacology, 1999
We have previously reported that intravenous (I.V.) administrations of 0.5-1.0 mg/kg of amphetami... more We have previously reported that intravenous (I.V.) administrations of 0.5-1.0 mg/kg of amphetamine in the absence of any environmental stimuli predictive of drug administration failed to induce psychomotor sensitization whereas the same drug did produce robust sensitization when given in association with environmental novelty. These results were obtained by studying rotational behavior in animals with a unilateral 6-OHDA lesion of the mesostriatal dopamine system. The purpose of this study was to determine if environmental novelty has a similar effect on sensitization to the locomotor activating effects of amphetamine in neurologically intact rats. Rats were implanted with I.V. catheters and divided in four groups. Two groups were housed in locomotor activity cages and given seven consecutive I.V. infusions of either saline (SAL-HOME group) or 0.375 mg/kg of amphetamine (AMPH-HOME group), using a remotely activated delivery system. Simultaneously, the other two groups were transported to the test cages and given the same treatment (SAL-NOVEL and AMPH-NOVEL groups). After one week withdrawal, all groups were given an amphetamine challenge (0.375 mg/kg, I.V.). Amphetamine sensitization developed when the drug was administered under NOVEL conditions, as indicated by a progressive increase in ampheatmine-induced locomotor activity over test sessions and by a greater response to the amphetamine challenge in the AMPH-pretreated versus the SAL-pretreated group. In contrast, no sensitization was observed under HOME conditions. Similar results were obtained with the analysis of vertical activity. [ Neuropsychopharmacology 20: 533-541, 1999] © 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
Behavioural Brain Research, 1997
The hypothesis that the combined activation of D1 and D2 dopaminergic receptors is instrumental i... more The hypothesis that the combined activation of D1 and D2 dopaminergic receptors is instrumental in inducing amphetamine (AMPH)-mediated hyperdipsia was tested in rats. The D1 agonist SKF-38393 (SKF) and the D2 agonist quinpirole (QNP) were i.p. injected, alone or in combination, to male rats for 10 days. After 2 days of wash-out, a single dose of AMPH (3 mg/kg) was administered. Intake of water and food and diuresis were daily measured at 2, 5 and 24 h. In two further experiments the higher dose of QNP (0.56 mg/kg) was given with two different doses of the D1 antagonist SCH-23390 (SCH), or, respectively, of the peripheral D2 antagonist domperidone (DMP). In a fourth experiment, the possibility that QNP, given alone or in combination with SKF, produces an AMPH-like internal state was evaluated by using a drug-discrimination paradigm. Results show that chronic administration of QNP produced a significant increase of 24 h water intake that was reinstated by AMPH. This QNP effect was only partially prevented by DMP, suggesting a main central mechanism of action. By itself D1 receptor manipulation did not affect water intake, but influenced QNP polydipsia that, accordingly, was enhanced by the lower dose of SKF (0.3 mg/kg) and inhibited by the lower dose of SCH (0.01 mg/kg). In rats trained to discriminate AMPH from solvent, QNP partially generalized for the AMPH stimulus, an effect that was potentiated by SKF. In conclusion, a D1-modulated sensitization of D2 dopaminergic mechanisms is probably involved in AMPH-induced hyperdipsia.
Behavioural Brain Research, 1998
Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances... more Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances the analgesic effects of morphine (MOR). Thus, it is possible that full psychomotor stimulant potency is not required to increase the analgesic action of opiates. The validity of this assumption is here tested by studying the ability of (-)-norpseudoephedrine (NPE), an enantiomer of phenylpropanolamine and a metabolite of cathinone, to influence both the analgesic effects of MOR and its discriminative stimulus properties. In mice NPE (5.6-10.0-17.0 mg/kg i.p.) did not prolong the latency to lick or to remove paws from a plate warmed at 54 degrees C. However, it significantly potentiated the analgesic effect of 3.2 mg/kg of MOR. These results were replicated in rats by use of the formalin test, which measures the numbers of hind paw flinches produced by injecting 50 microl of formalin into the dorsal surface of the paw. The higher dose of NPE (17 mg/kg) increased the effect of sub-analgesic doses of MOR (0.56 and 1.0 mg/kg). In rats trained to discriminate between 0.5 mg/kg of amphetamine and solvent in a two-lever operant behavior reinforced by water access. NPE induced a dose-dependent increment of drug lever responding from 0% at 1.0 mg/kg to 100% at 32.0 mg/kg. In contrast, NPE did not generalize for the MOR cue up to the dose of 56.0 mg/kg, which produced a substantial reduction of the response rate. However, when given in combination, NPE attenuated the discriminative effects of MOR and potentiated its inhibitory action on the response rate. These results exclude a direct action of NPE on the mu opiate system. In conclusion, NPE preserves amphetamine-like properties and these properties are probably responsible for the interaction of the drug with the analgesic and discriminative effects of MOR. Therefore, this study contradicts the assumption that the analgesic effects of MOR can be enhanced by a sympathomimetic drug that lacks significant psychostimulant actions.