Bert Siegfried - Academia.edu (original) (raw)
Papers by Bert Siegfried
Neuroscience, Jun 20, 1987
Behavioural Brain Research, May 1, 1983
PubMed, 1991
1. Microinjection of morphine (0.31, 1.25 and 5.0 micrograms) into the periaqueductal grey area (... more 1. Microinjection of morphine (0.31, 1.25 and 5.0 micrograms) into the periaqueductal grey area (PAG) of C57BL/6 (C57) and DBA/2 (DBA) mice increased the pain threshold in the tail-flick test. The highest dose also caused a behavioral reaction in both strains characterized by periods of immobility alternating with explosive motor behavior. 2. In the DBA strain, the analgesic effect was demonstrated with all doses of morphine, while in the C57 strain only the highest dose induced analgesia. 3. DBA mice presented a decrease in activity with the lowest dose of morphine, whereas in the C57 strain, this effect was obtained only with the highest dose of morphine. 4. These data corroborate at the PAG level the results of other studies which have shown that central and peripheral injections of morphine produce analgesia and alter motor activity in C57 and DBA strains. They also confirm that these two strains of mice present genotype-dependent differences in sensitivity to opioids as determined after injections of morphine into the PAG.
Physiology & Behavior, Oct 1, 1979
Lick triggered intracranial stimulation interferes with retrieval of conditioned taste aversion. ... more Lick triggered intracranial stimulation interferes with retrieval of conditioned taste aversion. PHYSIOL. BEHAV. 23(4) 625-631, 1979.wThe effect of brain stimulation on retrieval of conditioned taste aversion (CTA) to 0.15 M LiCl was investigated in 15 overtrained rats. The photoelecttrically detected licks at two drinking spouts delivering water or salt solutions, respectively, were used to trigger single electrical pulses, applied through implanted electrodes to basolateral amygdala or lateral hypothalamus. Current intensities not interfering with licking increased the number of licks required for recognition of the aversive fluid after spout switching from 1 or 2 to more than 5 and occasionally blocked gustatory discrimination completely. Discrimination was disrupted both by amygdalar and lateral hypothalamic stimulation of the same intensity, but amygdalar stimulation was more effective: interference was obtained from all amygdalar (n=21) but from only half of hypothalamic (n=17) stimulation points. The disruptive effects were cumulative. They were almost independent of the lick stimulus delay (1 to 100 ms) and often outlasted the period of stimulation for several min. The interfering effects of electrical stimulation are in accordance with the results of lesion studies indicating that the amygdala and the lateral hypothalamus participate in CTA retrieval, probably by mediating stimulus recognition and/or interruption of consummatory behavior.
Behavioral Neuroscience, 1987
The exposure of rats for 2 min to an open field, to a small box, or to inhibitory avoidance train... more The exposure of rats for 2 min to an open field, to a small box, or to inhibitory avoidance training in the small box was followed by a mild analgesia measured by the tail-flick method. The analgesia was observed as soon as 10 s after the exposure and lasted between 10 and 30 min. It was not observed in animals previously made familiar with the test situation, and it was reversed by the administration of naltrexone (0.1 mg/kg). The data suggest that novelty per se is a sufficient stimulus to activate an opioid-mediated analgesic stimulus.
Behavioural Processes, 1985
Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.], 1988
1. Recent evidence suggests that treatments given after training may influence memory in two ways... more 1. Recent evidence suggests that treatments given after training may influence memory in two ways: by becoming themselves incorporated to the experience, or by altering post-training mechanisms involved in the storage of the experience. The two processes may be called consolidation. 2. Some endogenous substances that are normally released during or after training (brain beta-endorphin; the peripheral stress hormones, ACTH, epinephrine and vasopressin) appear to be of particular importance. Their effect may become incorporated to the experiences as a conditioned stimulus (CS), generating state dependency. The effect of beta-endorphin appears to be physiological, since the substance is released by novel experiences. 3. Post-event information provided by other training experiences, in rats, or by comments or leading words, in humans, may also incorporate to the experiences, altering their content qualitatively or quantitatively. 4. A variety of substances including the stress hormones ...
Brain Research, May 1, 1979
The degree of the contralateral sensory neglect in rats with unilateral 6-OHDA lesions of substan... more The degree of the contralateral sensory neglect in rats with unilateral 6-OHDA lesions of substantia nigra was assessed by a conditioning procedure, employing lateralized CS. In the first experiment visual neglect (revealed by failure of the visually elicited placing reaction contralateral to the lesion) was shown to be accompanied by slower acquisition of a brightness discrimination task. The impairment was due to ipsilateral turning tendency rather then to visual deficit, however, since monocular relearning yielded equal savings with the ipsilateral and contralateral eyes. The second experiment showed that rats anesthetized with urethane reacted to noxious skin stimulation contralateral to the lesion with shorter-lasting EEG arousal than to ipsilateral stimulation of the same intensity. The electrophysiological asymmetry could be compensated by classical conditioning, i.e. by pairing habituated tactile stimuli with noxious tail shock. The conditioned arousal reaction could be elicited with the same efficiency from the neglected and intact body surface. It is concluded that neglect is due neither to a sensory nor to a motor failure, but that 6-OHDA lesions of substantia nigra in one hemisphere reduce the arousing efficiency of unconditioned stimuli and interfere with sensorimotor integrating mechanisms on the side contralateral to the lesion. Compensation of the neglect by conditioning indicates that the role of the nigrostriatal system can be partly substituted by other circuits.
Neuroscience, 1980
Unilateral intracranial administration of colchicine was used to interfere with the lateralized r... more Unilateral intracranial administration of colchicine was used to interfere with the lateralized reaching-for-food habit ('handedness') in rats. Epidural application of colchicine (500 pg/lO ~1) over the motor cortex contralateral to the preferred forepaw caused a partial blockade of reaching, culminating after 34 days and recovering after 7-10 days. The same amount of colchicine applied on the occipital cortex or on the motor cortex ipsilateral to the preferred forepaw did not affect reaching. Injection of colchicine (2 pgg/2 ~1) into the contralateral substantia nigra caused an almost complete impairment of reaching on Days 2-5. Recovery started on Day 6 but the initial performance level was not attained even 2 weeks after the injection. Blockade of reaching induced by the injection of colchicine (5 pg/5 ~1) into the contralateral caudate nucleus had a similar intensity and time course but recovery was faster. Histological examination revealed signs of partial tissue damage up to 500 pm from the site of injection. The results confirm the feasibility of using colchicine for reversible blockade of discrete brain areas but indicate at the same time that some of the effects of chochicine are irreversible.
The Biology of Aggression, 1981
Physiology & Behavior, 1988
Differences in locomotor activity in the open field were found between individually and group-hou... more Differences in locomotor activity in the open field were found between individually and group-housed rats (isol greater than soc). Daily handling, initiated at postnatal day 1, was without effect in group-housed rats but prevented the isolation-induced hyperactivity. For tail-flick latency, strikingly similar differences (isol greater than soc; prevention by handling) have been observed. The isolation-induced aberrations in both locomotor reactivity in a novel environment and in pain sensitivity could be reversed by subsequent resocialization. This indicates that the altered sensitivities to external stimuli are caused by the environmental manipulation.
Mice of two inbred strains (C57BL/6, DBA/2) were defeated by an aggressive conspecific and change... more Mice of two inbred strains (C57BL/6, DBA/2) were defeated by an aggressive conspecific and changes in nociception and behavior (submissive postures/escape) were recorded. The results suggest that defeat-induced analgesia in DBA mice interferes negatively with processing of the aversive experience, while the absence of nociceptive changes upon defeat in C57 mice enhances adaptation via behavioral responses.
Behavioural Brain Research, 1985
Physiology & Behavior, 1989
The present paper describes the development and application of an enzyme-linked immunosorbent ass... more The present paper describes the development and application of an enzyme-linked immunosorbent assay (ELISA) for the assessment of beta-endorphin-like immunoreactivity (beta-ELIR) level in the hypothalamus, the periaqueductal grey (PAG) and the pituitary of DBA/2 mice that were subjected to mild social stress (aggressive confrontation). After confrontation these subjects showed elevated tail-flick latencies (TFL) when compared to controls, a finding that indicates stress-induced analgesia (SIA). A positive correlation was found between individual TFLs and beta-ELIR levels in the PAG but not in the hypothalamus and the pituitary. These results suggest that individual baseline PAG beta-ELIR levels may be taken as a predictor of high degrees of stress-induced analgesia.
Advances in Behavioral Biology, 1985
Mice react upon defeat with defense reactions which can be considered as naturally occurring avoi... more Mice react upon defeat with defense reactions which can be considered as naturally occurring avoidance responses. In an attempt to characterize the effect of genotype on adaptive capabilities of interacting male mice, a learning model was used, which measures behavioral reactions in two inbred strains of mice (C57BL/6 and DBA/2) during defeat and 24 h later during a confrontation with a nonaggressive opponent.
Behavioural Brain Research, 1981
In order to investigate mechanisms of isolation-induced aggressive behavior, inbred mice of the C... more In order to investigate mechanisms of isolation-induced aggressive behavior, inbred mice of the C57BL/6 and DBA/2 strains were individually housed over a period of 8 weeks. In the DBA/2 strain only, isolation was followed by a clear increase in activity (Animex), reactivity (reactions upon tactile body stimulation), excitability (duration of EEG desynchronization elicited by tactile stimulation of the thorax area under urethane anesthesia) and intermale aggression (biting and fighting responses). The use of inbred strains of mice proved to be a useful tool for the examination of the relationship between various parameters. It is concluded that there are no clear correlations between activity, reactivity and aggressive behavior and that the resulting aggressive responses in the DBA/2 strain are likely due to the increase of excitability.
Behavioral and Neural Biology, Jul 31, 1989
In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradi... more In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradigm) were investigated in attacked, DBA/2 and C57BL/6, mice. During training, exposure of test animals to 10 or 30 bites by an aggressive, isolated ICR mouse situated in the dark half of a bright/dark conditioning box induced a significantly higher social conflict analgesia in DBA than in C57 mice. Naltrexone (0.5 and 2.0 mg/kg) reduced this response in DBA mice that received 30, but not 10, bites and was ineffective in C57 mice. This points to different, opioid versus naltrexone-insensitive nonopioid, analgesic mechanisms. During place choice testing in the same box 24 h later, DBA mice that had received 30, but not 10, bites showed a significant, naltrexone-reversible, avoidance of the attack place. No place avoidance learning was observed in C57 mice. The data provided unequivocal evidence that place avoidance learning was a result of associative conditioning, in that neither pairing nor social conflict per se significantly changed the preference for the dark side seen in experimentally naive DBA mice. Antagonism of place avoidance conditioning was observed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation for the naltrexone-induced impairment. Individual correlational analysis in saline-injected, attacked DBA mice revealed a negative relationship between the analgesic state immediately after training and the avoidance of attack place during testing. In summary, the results suggest strain-dependent analgesic and learning mechanisms and indicate that endogenous opioids released in attacked DBA mice support pain inhibition and modulate the memorization of attack place by their analgesic effects, as well as by mechanisms independent of pain inhibitory systems.
European Journal of Pharmacology, Sep 13, 1989
Microinjections of N-methyl-D-aspartate (NMDA, 0.1 and 1.0 nmol) into the periaqueductal grey (PA... more Microinjections of N-methyl-D-aspartate (NMDA, 0.1 and 1.0 nmol) into the periaqueductal grey (PAG) of the mouse resulted in potential antinociception. In a social conflict situation, attacked mice exhibited a marked analgesia that was prevented by prior injection of the competitive NMDA antagonist, AP-7 (2.0 nmol) or naloxone (6.0 nmol) into the PAG and also by i.p. injection of the non-competitive NMDA antagonist, MK-801 (33 nmol). These results demonstrate that NMDA receptors are involved in endogenous analgesic mechanisms activated by stress.
Neuroscience, Jun 20, 1987
Behavioural Brain Research, May 1, 1983
PubMed, 1991
1. Microinjection of morphine (0.31, 1.25 and 5.0 micrograms) into the periaqueductal grey area (... more 1. Microinjection of morphine (0.31, 1.25 and 5.0 micrograms) into the periaqueductal grey area (PAG) of C57BL/6 (C57) and DBA/2 (DBA) mice increased the pain threshold in the tail-flick test. The highest dose also caused a behavioral reaction in both strains characterized by periods of immobility alternating with explosive motor behavior. 2. In the DBA strain, the analgesic effect was demonstrated with all doses of morphine, while in the C57 strain only the highest dose induced analgesia. 3. DBA mice presented a decrease in activity with the lowest dose of morphine, whereas in the C57 strain, this effect was obtained only with the highest dose of morphine. 4. These data corroborate at the PAG level the results of other studies which have shown that central and peripheral injections of morphine produce analgesia and alter motor activity in C57 and DBA strains. They also confirm that these two strains of mice present genotype-dependent differences in sensitivity to opioids as determined after injections of morphine into the PAG.
Physiology & Behavior, Oct 1, 1979
Lick triggered intracranial stimulation interferes with retrieval of conditioned taste aversion. ... more Lick triggered intracranial stimulation interferes with retrieval of conditioned taste aversion. PHYSIOL. BEHAV. 23(4) 625-631, 1979.wThe effect of brain stimulation on retrieval of conditioned taste aversion (CTA) to 0.15 M LiCl was investigated in 15 overtrained rats. The photoelecttrically detected licks at two drinking spouts delivering water or salt solutions, respectively, were used to trigger single electrical pulses, applied through implanted electrodes to basolateral amygdala or lateral hypothalamus. Current intensities not interfering with licking increased the number of licks required for recognition of the aversive fluid after spout switching from 1 or 2 to more than 5 and occasionally blocked gustatory discrimination completely. Discrimination was disrupted both by amygdalar and lateral hypothalamic stimulation of the same intensity, but amygdalar stimulation was more effective: interference was obtained from all amygdalar (n=21) but from only half of hypothalamic (n=17) stimulation points. The disruptive effects were cumulative. They were almost independent of the lick stimulus delay (1 to 100 ms) and often outlasted the period of stimulation for several min. The interfering effects of electrical stimulation are in accordance with the results of lesion studies indicating that the amygdala and the lateral hypothalamus participate in CTA retrieval, probably by mediating stimulus recognition and/or interruption of consummatory behavior.
Behavioral Neuroscience, 1987
The exposure of rats for 2 min to an open field, to a small box, or to inhibitory avoidance train... more The exposure of rats for 2 min to an open field, to a small box, or to inhibitory avoidance training in the small box was followed by a mild analgesia measured by the tail-flick method. The analgesia was observed as soon as 10 s after the exposure and lasted between 10 and 30 min. It was not observed in animals previously made familiar with the test situation, and it was reversed by the administration of naltrexone (0.1 mg/kg). The data suggest that novelty per se is a sufficient stimulus to activate an opioid-mediated analgesic stimulus.
Behavioural Processes, 1985
Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.], 1988
1. Recent evidence suggests that treatments given after training may influence memory in two ways... more 1. Recent evidence suggests that treatments given after training may influence memory in two ways: by becoming themselves incorporated to the experience, or by altering post-training mechanisms involved in the storage of the experience. The two processes may be called consolidation. 2. Some endogenous substances that are normally released during or after training (brain beta-endorphin; the peripheral stress hormones, ACTH, epinephrine and vasopressin) appear to be of particular importance. Their effect may become incorporated to the experiences as a conditioned stimulus (CS), generating state dependency. The effect of beta-endorphin appears to be physiological, since the substance is released by novel experiences. 3. Post-event information provided by other training experiences, in rats, or by comments or leading words, in humans, may also incorporate to the experiences, altering their content qualitatively or quantitatively. 4. A variety of substances including the stress hormones ...
Brain Research, May 1, 1979
The degree of the contralateral sensory neglect in rats with unilateral 6-OHDA lesions of substan... more The degree of the contralateral sensory neglect in rats with unilateral 6-OHDA lesions of substantia nigra was assessed by a conditioning procedure, employing lateralized CS. In the first experiment visual neglect (revealed by failure of the visually elicited placing reaction contralateral to the lesion) was shown to be accompanied by slower acquisition of a brightness discrimination task. The impairment was due to ipsilateral turning tendency rather then to visual deficit, however, since monocular relearning yielded equal savings with the ipsilateral and contralateral eyes. The second experiment showed that rats anesthetized with urethane reacted to noxious skin stimulation contralateral to the lesion with shorter-lasting EEG arousal than to ipsilateral stimulation of the same intensity. The electrophysiological asymmetry could be compensated by classical conditioning, i.e. by pairing habituated tactile stimuli with noxious tail shock. The conditioned arousal reaction could be elicited with the same efficiency from the neglected and intact body surface. It is concluded that neglect is due neither to a sensory nor to a motor failure, but that 6-OHDA lesions of substantia nigra in one hemisphere reduce the arousing efficiency of unconditioned stimuli and interfere with sensorimotor integrating mechanisms on the side contralateral to the lesion. Compensation of the neglect by conditioning indicates that the role of the nigrostriatal system can be partly substituted by other circuits.
Neuroscience, 1980
Unilateral intracranial administration of colchicine was used to interfere with the lateralized r... more Unilateral intracranial administration of colchicine was used to interfere with the lateralized reaching-for-food habit ('handedness') in rats. Epidural application of colchicine (500 pg/lO ~1) over the motor cortex contralateral to the preferred forepaw caused a partial blockade of reaching, culminating after 34 days and recovering after 7-10 days. The same amount of colchicine applied on the occipital cortex or on the motor cortex ipsilateral to the preferred forepaw did not affect reaching. Injection of colchicine (2 pgg/2 ~1) into the contralateral substantia nigra caused an almost complete impairment of reaching on Days 2-5. Recovery started on Day 6 but the initial performance level was not attained even 2 weeks after the injection. Blockade of reaching induced by the injection of colchicine (5 pg/5 ~1) into the contralateral caudate nucleus had a similar intensity and time course but recovery was faster. Histological examination revealed signs of partial tissue damage up to 500 pm from the site of injection. The results confirm the feasibility of using colchicine for reversible blockade of discrete brain areas but indicate at the same time that some of the effects of chochicine are irreversible.
The Biology of Aggression, 1981
Physiology & Behavior, 1988
Differences in locomotor activity in the open field were found between individually and group-hou... more Differences in locomotor activity in the open field were found between individually and group-housed rats (isol greater than soc). Daily handling, initiated at postnatal day 1, was without effect in group-housed rats but prevented the isolation-induced hyperactivity. For tail-flick latency, strikingly similar differences (isol greater than soc; prevention by handling) have been observed. The isolation-induced aberrations in both locomotor reactivity in a novel environment and in pain sensitivity could be reversed by subsequent resocialization. This indicates that the altered sensitivities to external stimuli are caused by the environmental manipulation.
Mice of two inbred strains (C57BL/6, DBA/2) were defeated by an aggressive conspecific and change... more Mice of two inbred strains (C57BL/6, DBA/2) were defeated by an aggressive conspecific and changes in nociception and behavior (submissive postures/escape) were recorded. The results suggest that defeat-induced analgesia in DBA mice interferes negatively with processing of the aversive experience, while the absence of nociceptive changes upon defeat in C57 mice enhances adaptation via behavioral responses.
Behavioural Brain Research, 1985
Physiology & Behavior, 1989
The present paper describes the development and application of an enzyme-linked immunosorbent ass... more The present paper describes the development and application of an enzyme-linked immunosorbent assay (ELISA) for the assessment of beta-endorphin-like immunoreactivity (beta-ELIR) level in the hypothalamus, the periaqueductal grey (PAG) and the pituitary of DBA/2 mice that were subjected to mild social stress (aggressive confrontation). After confrontation these subjects showed elevated tail-flick latencies (TFL) when compared to controls, a finding that indicates stress-induced analgesia (SIA). A positive correlation was found between individual TFLs and beta-ELIR levels in the PAG but not in the hypothalamus and the pituitary. These results suggest that individual baseline PAG beta-ELIR levels may be taken as a predictor of high degrees of stress-induced analgesia.
Advances in Behavioral Biology, 1985
Mice react upon defeat with defense reactions which can be considered as naturally occurring avoi... more Mice react upon defeat with defense reactions which can be considered as naturally occurring avoidance responses. In an attempt to characterize the effect of genotype on adaptive capabilities of interacting male mice, a learning model was used, which measures behavioral reactions in two inbred strains of mice (C57BL/6 and DBA/2) during defeat and 24 h later during a confrontation with a nonaggressive opponent.
Behavioural Brain Research, 1981
In order to investigate mechanisms of isolation-induced aggressive behavior, inbred mice of the C... more In order to investigate mechanisms of isolation-induced aggressive behavior, inbred mice of the C57BL/6 and DBA/2 strains were individually housed over a period of 8 weeks. In the DBA/2 strain only, isolation was followed by a clear increase in activity (Animex), reactivity (reactions upon tactile body stimulation), excitability (duration of EEG desynchronization elicited by tactile stimulation of the thorax area under urethane anesthesia) and intermale aggression (biting and fighting responses). The use of inbred strains of mice proved to be a useful tool for the examination of the relationship between various parameters. It is concluded that there are no clear correlations between activity, reactivity and aggressive behavior and that the resulting aggressive responses in the DBA/2 strain are likely due to the increase of excitability.
Behavioral and Neural Biology, Jul 31, 1989
In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradi... more In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradigm) were investigated in attacked, DBA/2 and C57BL/6, mice. During training, exposure of test animals to 10 or 30 bites by an aggressive, isolated ICR mouse situated in the dark half of a bright/dark conditioning box induced a significantly higher social conflict analgesia in DBA than in C57 mice. Naltrexone (0.5 and 2.0 mg/kg) reduced this response in DBA mice that received 30, but not 10, bites and was ineffective in C57 mice. This points to different, opioid versus naltrexone-insensitive nonopioid, analgesic mechanisms. During place choice testing in the same box 24 h later, DBA mice that had received 30, but not 10, bites showed a significant, naltrexone-reversible, avoidance of the attack place. No place avoidance learning was observed in C57 mice. The data provided unequivocal evidence that place avoidance learning was a result of associative conditioning, in that neither pairing nor social conflict per se significantly changed the preference for the dark side seen in experimentally naive DBA mice. Antagonism of place avoidance conditioning was observed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation for the naltrexone-induced impairment. Individual correlational analysis in saline-injected, attacked DBA mice revealed a negative relationship between the analgesic state immediately after training and the avoidance of attack place during testing. In summary, the results suggest strain-dependent analgesic and learning mechanisms and indicate that endogenous opioids released in attacked DBA mice support pain inhibition and modulate the memorization of attack place by their analgesic effects, as well as by mechanisms independent of pain inhibitory systems.
European Journal of Pharmacology, Sep 13, 1989
Microinjections of N-methyl-D-aspartate (NMDA, 0.1 and 1.0 nmol) into the periaqueductal grey (PA... more Microinjections of N-methyl-D-aspartate (NMDA, 0.1 and 1.0 nmol) into the periaqueductal grey (PAG) of the mouse resulted in potential antinociception. In a social conflict situation, attacked mice exhibited a marked analgesia that was prevented by prior injection of the competitive NMDA antagonist, AP-7 (2.0 nmol) or naloxone (6.0 nmol) into the PAG and also by i.p. injection of the non-competitive NMDA antagonist, MK-801 (33 nmol). These results demonstrate that NMDA receptors are involved in endogenous analgesic mechanisms activated by stress.