RAPHE 5-HT1A AUTORECEPTORS, BUT NOT POSTSYNAPTIC 5-HT1A RECEPTORS OR BETA-ADRENOCEPTORS, RESTRAIN THE CITALOPRAM-INDUCED INCREASE IN EXTRACELLULAR 5-HYDROXYTRYPTAMINE IN-VIVO

In vivo microdialysis in rat ventral hippocampus was used (i) to verif y the importance of 5-HT1A autoreceptors in the raphe as targets for d rugs that enhance the citalopram-induced elevation of forebrain 5-hydr oxytryptamine (5-HT), and (ii) to further examine the specificity of(- )-penbutolol in this regard. The selective 5-HT1A receptor antagonist WAY100635 (s.c., or intra-raphe) or the mixed 5-HT1A/1B/beta-adrenocep tor antagonist (-)-penbutolol (s.c.), potentiated the citalopram-induc ed 5-HT rise, whereas local 'reverse' dialysis of WAY100635 into the v entral hippocampus did not. Furthermore, the (-)-penbutolol-induced au gmentation proved stereoselective and not mediated by beta-adrenocepto rs (no effect of s.c. (+)-penbutolol, or beta(1)- and beta(2)-adrenoce ptor blockers (betaxolol, ICI118.551)). These data provide direct evid ence that increased stimulation of 5-HT1A autoreceptors in the midbrai n raphe impedes the effect of citalopram on forebrain extracellular 5- HT, whereas neither postsynaptic 5-HT1A receptors nor beta-adrenocepto rs appear to be involved.