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Pharmacological characterization of 8‐OH‐DPAT‐induced inhibition of rat hippocampal 5‐HT release in vivo as measured by microdialysis
Author(s) -
Sharp Trevor,
Bramwell Steven R.,
Hjorth Stephan,
GrahameSmith David G.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb14630.x
Subject(s) - ritanserin , methysergide , metergoline , microdialysis , chemistry , agonist , receptor antagonist , 5 ht receptor , endocrinology , pindolol , medicine , idazoxan , pharmacology , ketanserin , antagonist , yohimbine , receptor , serotonin , prazosin , biochemistry , extracellular
1 We have previously found that the putative 5‐HT 1A agonist 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) decreases hippocampal 5‐hydroxytryptamine (5‐HT) release in the anaesthetized rat, as measured by brain microdialysis. The present study attempted to characterize the receptor involved in this response using a range of monoamine receptor antagonists. 2 The classical 5‐HT receptor antagonists, metergoline (5 mg kg −1 s.c.), methysergide (10 mg kg −1 s.c.) and methiothepin (10 mgkg −1 s.c.) each reduced dialysate levels of 5‐HT which complicated their use as antagonists in these experiments. Nevertheless, pretreatment with metergoline but not methiothepin and methysergide partially reduced the 5‐HT response to a maximally effective dose of 8‐OH‐DPAT (0.25 mg kg −1 s.c.). 3 The mixed 5‐HT 1 /β‐adrenoceptor antagonist pindolol (8 mg kg −1 s.c.) was without effect on spontaneous 5‐HT output but attenuated the effect of both maximally (0.25 mg kg −1 s.c.) and submaximally (0.05 mg kg −1 s.c.) effective dose of 8‐OH‐DPAT. In comparison, propranolol (10 mg kg −1 s.c.) did not affect 5‐HT output when injected alone and did not alter the response to 8‐OH‐DPAT (0.25 mg kg −1 s.c.). 4 The 5‐HT 2 receptor antagonist ritanserin (0.2 mg kg −1 s.c.) and the 5‐HT 3 receptor antagonist BRL 43694 (0.5 mg kg −1 s.c.) neither altered 5‐HT output alone nor significantly changed the response to 8‐OH‐DPAT (0.25 mg kg −1 s.c.). 5 The 8‐OH‐DPAT (0.25 mg kg −1 s.c.) response was not affected by pretreatment with either the dopamine D 2 ‐receptor antagonist sulpiride (10 mg kg −1 s.c.) or the α 1 /α 2 ‐adrenoceptor antagonist phentolamine (10 mg kg −1 s.c.). 6 We conclude from these data that the decrease of hippocampal 5‐HT output induced by 8‐OH‐DPAT does not involve 5‐HT 2 , 5‐HT 3 , adrenoceptors or dopamine D 2 ‐receptors and that activation of a 5‐HT 1 class of receptor seems probable. Full classification of the 8‐OH‐DPAT response awaits development of a suitably selective 5‐HT 1 receptor antagonist with low intrinsic activity at the somatodendritic 5‐HT autoreceptor.