Diazepam withdrawal increases [3H]-5-HT release from rat amygdaloid slices.
The release of [3H]-5-HT and [14C]-GABA from hippocampal and amygdaloid slices was studied in a group of rats in which an anxiogenic response had been found on withdrawal of chronic diazepam treatment (2 mg/kg/day for 21 days). Basal release and uptake of [3H]-5-HT and [14C]-GABA and K(+)-evoked release of [14C]-GABA were not significantly changed in either brain region following diazepam withdrawal. However, there was a significant increase in K(+)-evoked [3H]-5-HT release from the amygdala, but not from the hippocampal, slices. These results demonstrate that increased 5-HT release from the hippocampus is not necessary to mediate the anxiogenic withdrawal response, and that raised 5-HT release in the amygdala may be sufficient to mediate this response. The results are discussed with respect to conditions, such as noise during diazepam treatment, that might produce regionally specific changes in 5-HT tone and hence modify the pattern of changes found during diazepam withdrawal.
Fernandes
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Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London.
Andrews
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D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000523:psychology; D003975:Diazepam / Q000009:adverse effects*; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018377:Neurotransmitter Agents; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D011188:Potassium