(-)-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 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.
Assie
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Neurobiology Division II, Centre de Recherche Pierre Fabre, Castres, France.
Koek
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015784:Betaxolol / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D010869:Pindolol / Q000378:metabolism / Q000494:pharmacology*; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013876:Thiophenes
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011985:Receptors, Serotonin; D013876:Thiophenes; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C005632:tertatolol; D010869:Pindolol; D015784:Betaxolol