The interaction of serotonin depletion with anxiolytics and antidepressants on reticular-elicited hippocampal RSA.
Hippocampal rhythmical slow activity (RSA) can be elicited by stimulation of the midbrain reticular formation. Buspirone, chlordiazepoxide and imipramine are all anxiolytic and have all been shown to decrease the frequency of RSA. All these compounds have been suggested to affect, directly or indirectly, 5-HT metabolism and function. The present experiments tested the possibility that buspirone, chlordiazepoxide and imipramine reduce RSA frequency via 5-HT1A autoreceptors. Rats received buspirone (10 mg/kg), chlordiazepoxide (5 mg/kg) and imipramine (30 mg/kg) after 5-HT depletion with p-chlorophenylalanine (pCPA, 100 mg/kg/day for 3 days or 350 mg/kg/day for 2 days) or after pretreatment with 5-HTP (40 mg/kg, to replete 5-HT) as well as pCPA. The frequency-reducing effects produced by buspirone and chlordiazepoxide were unchanged by either dose of pCPA, whereas the frequency-reducing effect of imipramine was completely eliminated by the high dose of pCPA. Pindolol, but not beta-blockers (a combination of metoprolol and ICI118,551), was able to block the effect of imipramine on RSA frequency. Pindolol has been reported to block the effects of buspirone but not chlordiazepoxide. These data suggest that: (1) buspirone obtains its frequency-reducing effects via pre- or post-synaptic 5-HT1A receptors rather than 5-HT1A autoreceptors; (2) chlordiazepoxide obtains its frequency-reducing effect via benzodiazepine receptors and GABA with no direct or indirect involvement of 5-HT systems; and (3) imipramine obtains its frequency-reducing effect by increasing the availability of 5-HT at 5-HT1A receptors which are not autoreceptors.
Zhu
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Department of Psychology, University of Otago, Dunedin, New Zealand.
McNaughton
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology; D003565:Cytidine Diphosphate / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012154:Reticular Formation / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D013826:Theta Rhythm / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D012701:Serotonin; D003565:Cytidine Diphosphate; D010869:Pindolol; D007099:Imipramine; D002065:Buspirone