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B L Jacobs

Publications and source records attributed to B L Jacobs.

At least 181 records · Page 10Linked to original sources

LSD acts synergistically with serotonin depletion: evidence from behavioral studies in cats.

Administration of LSD (100 mug/kg, IP) or the serotonin depleting drug p-chlorophenylalanine (150 mg/kg/day for 5 days) both induce dramatic behavioral changes which include the common stereotyped responses of rapid flicking movements of the limbs and abortive attempts at grooming. The combined action of LSD and p=chlorophenylalanine results in a marked increase in the occurrence of these behaviors, suggesting that LSD acts synergistically with serotonin depletion. These data therefore support the hypothesis that the behavioral effects of LSD may be attributable to its well known electrophysiological effect of depressing the activity of serotonin containing neurons. In addition, limb flicking and abortive grooming may serve as a useful behavioral model for studying the actions of LSD, since these behaviors are quantifiable, easily scored, and occur with an extremely low frequency in normal cats.

Amphetamine↗

Differential behavioral effects of lesions of the median or dorsal raphe nuclei in rats: open field and pain-elicited aggression.

Electrolytic lesions were placed in either the dorsal or median raphe nuclei of adult male albino rats. Both lesions produced significant reductions in forebrain serotonin levels. Lesions of the dorsal nucleus produced a long-lasting increase in pain-elicited aggression, whereas median lesions were without effect. By contrast, lesions of the median nucleus produced significant increases in open-field activity, which began immediately and lasted for at least 3 mo, whereas lesions of the dorsal nucleus had no such effect. Similarly, when animals with dorsal or sham lesions were tested in an open field and then given a brief noncontingent footshock, their open-field activity was markedly reduced on the following day. Median animals, however, showed little or no decrease in open-field activity on the day after footshock. These results suggest that the serotonin-containing neurons of the median raphe nucleus may exert an influence over the emotional responsivity of the rat. The overall results of these experiments extend our previous reports that lesions specific to the dorsal nucleus produce markedly different behavioral effects than lesions confined to the median nucleus. They also challenge the utility of manipulations that fail to take this into account, e.g., lesions of more than one nucleus or depletion of serotonin throughout the central nervous system.

Aggression↗

Behavioral evidence for supersensitivity following destruction of central serotonergic nerve terminals by 5,7-dihydroxytryptamine.

Previous studies have established that a complex behavioral syndrome--consisting of tremor, rigidity, hindlimb abduction. Straub tail, lateral head weaving and reciprocal forepaw treading--is a specific reflection of the activity of central serotonin receptors. This syndrome was utilized in the present study to test for supersensitivity in the central serotonergic system. Specific destruction of central serotonin nerve terminals by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT, 50 mug) in adult male rats pretreated with a catecholamine uptake blocking agent resulted in marked supersensitivity to serotonin precursors and agonists. The greatest degree of supersensitivity was observed in response to L-5-hydroxytryptophan, for which the ED50 for elicitation of the syndrome was 20% of the value for control rats. A lesser degree of supersensitivity was seen in response to L-tryptophan (following monoamine oxidase inhibition) and the direct-acting serotonin agonist, 5-methoxy-N,N-dimethyltryptamine, for which the ED50 was approximately 50% of the control value in both cases. Supersensitivity begins to develop within 24 hours and is relatively complete by 96 hours after 5,7-DHT. A marked subsensitivity to the serotonin releasing agent, fenfluramine, was found in 5,7-DHT-treated rats. In contrast to the marked supersensitivity to serotonin precursors and agonists which occurs following 5,7-DHT, chronic administration of a serotonin synthesis inhibitor, p-chlorophenylalanine (400 mg/kg every 3 days for a total of 24 days), did not produce supersensitivity to L-5-hydroxytryptophan or 5-methoxy-N,N-dimethyltryptamine. Possible pre- and postsynaptic mechanisms for the development of supersensitivity are discussed.

5-Hydroxytryptophan↗

Behavioral evidence for the stimulation of CNS serotonin receptors by high doses of LSD.

Systemic administration of lysergic acid diethylamide (LSD) to rats induces a behavioral syndrome--consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading--which is a reflection of increased activation of central serotonin receptors. Utilizing this behavioral measure, a marked supersensitivity to LSD was observed in rats whose serotonin nerve terminals had been selectively destroyed, and a dramatic tolerance to LSD was observed following its repeated administration to normal rats. These data provide direct evidence that LSD can stimulate CNS serotonin receptors to a degree which markedly affects behavior.

Animals↗

Hippocampal mediation of raphe lesion- and PCPA-induced hyperactivity in the rat.

These experiments provide a direct test of the hypothesis that median raphe lesion- or PCPA-induced hyperactivity in the rat is mediated specifically by the hippocampus. Previous studies had shown that a marked depletion of hippocampal serotonin accompanied median lesion-induced hyperactivity. In the present studies, aspiration of the anterodorsal hippocampus of adult male rats prior to median raphe lesions or PCPA administration abolished the ability of both of these treatments to produce locomotor hyperactivity in animals chronically housed in tilt cages. Control lesions of the overlying dorsal cortex and corpus callosum were ineffective in blocking the hyperactivity produced by these two treatments. The possibility that serotonin depletion-induced hyperactivity was dependent on the pituitary was excluded by the fact that PCPA effectively elevated the activity of hypophysectomized rats. These data indicate that serotonin depletion-induced hyperactivity in the rat is mediated by the hippocampus.

Animals↗

Single unit activity in the lateral amygdala of the cat during sleep and waking.

Neuronal activity of 58 cells in the lateral nucleus of the amygdala of freely moving cats was studied across stages of sleep-wakefulness. In general, these units were very slow firing in all states (mean discharge rate less than 1 spike/sec) with the highest rates typically observed during slow wave sleep and paradoxical sleep. Most units tended to show some bursting activity during all states. The bursting during paradoxical sleep was not temporally correlated with the phasic activity characteristic of that state. These results corroborate and extend previous studies of the basal amygdaloid nuclei.

Acoustic Stimulation↗

Fluoridation.

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Fluoridation↗