THE INTERACTION OF SEROTONIN DEPLETION WITH ANXIOLYTICS AND ANTIDEPRESSANTS ON RETICULAR-ELICITED HIPPOCAMPAL RSA

Hippocampal rhythmical slow activity (RSA) can be elicited by stimulat ion of the midbrain reticular formation. Buspirone, chlordiazepoxide a nd imipramine are all anxiolytic and have all been shown to decrease t he frequency of RSA. All these compounds have been suggested to affect , directly or indirectly, 5-HT metabolism and function. The present ex periments tested the possibility that buspirone, chlordiazepoxide and imipramine reduce RSA frequency via 5-HTlA autoreceptors. Rats receive d buspirone (10 mg/kg), chlordiazepoxide (5 mg/kg) and imipramine (30 mg/kg) after 5-HT depletion with p-chlorophenylalanine (pCPA, 100 mg/k g/day for 3 days or 350 mg/kg/day for 2 days) or after pretreatment wi th 5-HTP (40 mg/kg, to replete 5-HT) as well asp CPA. The frequency-re ducing effects produced by buspirone and chlordiazepoxide were unchang ed by either dose of pCPA, whereas the frequency-reducing effect of im ipramine was completely eliminated by the high dose of pCPA. Pindolol, but not beta-blockers (a combination of metoprolol and ICI118 551), w as able to block the effect of imipramine on RSA frequency. Pindolol h as been reported to block the effects of buspirone but not chlordiazep oxide. These data suggest that: (1) buspirone obtains its frequency-re ducing effects via pre- or post-synaptic 5-HTlA receptors rather than 5-HTlA autoreceptors; (2) chlordiazepoxide obtains its frequency-reduc ing effect via benzodiazepine receptors and GABA with no direct or ind irect involvement of 5-HT systems; and (3) imipramine obtains its freq uency-reducing effect by increasing the availability of 5-HT at 5-HTlA receptors which are not autoreceptors.