(-)-pindolol and (+/-)-tertatolol affect rat hippocampal 5-HT levels through mechanisms involving not only 5-HT1A, but also 5-HT1B receptors.

ABSTRACT

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 properties, on extracellular 5-HT levels in the ventral hippocampus of chloral hydrate-anaesthetized rats. These effects were compared with those 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 after systemic administration (at 2.5 and 10 mg/kg s.c.), but also when perfused locally through the dialysis probe (at a concentration of 10 microM). At doses equal to or lower than those that increased 5-HT when given alone, (-)-pindolol and (+/-)-tertatolol inhibited the decrease of extracellular 5-HT levels induced by 8-OH-DPAT. At higher doses, however, (-)-pindolol and (+/-)-tertatolol were less able to reverse these effects of 8-OD-DPAT. The selective beta 1-adrenoceptor antagonist, (+/-)-betaxolol, did not alter 5-HT levels, either when given alone or when given together with 8-OD-DPAT. Although the antagonism of the 8-OH-DPAT-induced decrease of 5-HT levels by (-)-pindolol and (+/-)-tertatolol is likely to be related to their 5-HT1A antagonist properties, their ability to increase extracellular 5-HT levels when given alone may involve interactions with 5-HT1B receptors at hippocampal 5-HT terminals.