Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

1. We have previously found that the putative 5-HT1A 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 mg kg-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/beta-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-HT2 receptor antagonist ritanserin (0.2 mg kg-1 s.c.) and the 5-HT3 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-' s.c.) response was not affected by pretreatment with either the dopamine D2-receptor antagonist sulpiride (10mgkg-1 s.c.) or the alpha/alpha 2-adrenoceptor antagonist phentolamine (10mg kg-1 s.c.). 6. We conclude from these data that the decrease of hippocampal 5-HT output induced by 8-OHDPAT does not involve 5-HT2, 5-HT3, adrenoceptors or dopamine D2-receptors and that activation of a 5-HT1 class of receptor seems probable. Full classification of the 8-OH-DPAT response awaits development of a suitably selective 5-HT1 receptor antagonist with low intrinsic activity at the somatodendritic 5-HT autoreceptor.

Type

Journal article

Journal

Br J Pharmacol

Publication Date

11/1989

Volume

98

Pages

989 - 997

Keywords

8-Hydroxy-2-(di-n-propylamino)tetralin, Adrenergic beta-Antagonists, Anesthesia, Animals, Biogenic Monoamines, Dialysis, Hippocampus, Male, Naphthalenes, Rats, Rats, Inbred Strains, Receptors, Dopamine, Serotonin, Serotonin Antagonists, Tetrahydronaphthalenes