(-)-PINDOLOL AND (+ -)-TERTATOLOL AFFECT RAT HIPPOCAMPAL 5-HT LEVELS THROUGH MECHANISMS INVOLVING NOT ONLY 5-HT1A, BUT ALSO 5-HT1B RECEPTORS/

The present work examined, using in vivo microdialysis, the effects of 0.16-10 mg/kg of the beta-adrenoceptor antagonists, (-)-pindolol and (+/-)-tertatolol, which have additional 5-HT1A receptor antagonist pro perties, on extracellular 5-HT levels in the ventral hippocampus of ch loral hydrate-anaesthetized rats. These effects were compared with tho se observed when (-)-pindolol and (+/-)-tertatolol were given together with the 5-HT1A agonist 8-OH-DPAT (0.31 mg/kg i.p.). When given alone , (-)-pindolol and (+/-)-tertatolol increased 5-HT levels not only aft er systemic administration (at 2.5 and 10 mg/kg s.c.), but also when p erfused locally through the dialysis probe (at a concentration of 10 m u M). At doses equal to or lower than those that increased 5-HT when g iven alone, (-)-pindolol and (+/-)-tertatolol inhibited the decrease o f extracellular 5-HT levels induced by 8-OH-DPAT. At higher doses, how ever, (-)-pindolol and (+/-)-tertatolol were less able to reverse thes e effects of 8-OH-DPAT. The selective beta 1-adrenoceptor antagonist, (+/-)-betaxolol, did not alter 5-HT levels, either when given alone or when given together with 8-OH-DPAT. Although the antagonism of the 8- OH-DPAT-induced decrease of 5-HT levels by (-)-pindolol and (+/-)-tert atolol is likely to be related to their 5-HT1A antagonist properties, their ability to increase extracellular 5-HT levels when given alone m ay involve interactions with 5-HT1B receptors at hippocampal 5-HT term inals.