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-HTlA 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 asp CPA. 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-HTlA receptors rather than 5-HTlA 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-HTlA receptors which are not autoreceptors.
