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Evidence for depressant 5‐HT 1 ‐like receptors on rat brainstem neurones
Author(s) -
Davies Michael,
Wilkinson Lawrence S.,
Roberts Malcolm H.T.
Publication year - 1988
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.1476-5381.1988.tb11552.x
Subject(s) - metergoline , methysergide , ketanserin , 5 ht receptor , pharmacology , chemistry , receptor , serotonin , depressant , receptor antagonist , antagonist , agonist , ritanserin , 8 oh dpat , endocrinology , medicine , biochemistry
1 The technique of microiontophoresis was used to evaluate the contribution of 5‐HT 1 ‐like, 5‐HT 2 ‐ and 5‐HT 3 ‐receptors to the depressant effects of 5‐hydroxytryptamine (5‐HT) on neurones in the midline of the medullary brainstem of the rat in vivo . 2 Depressant responses to 5‐HT were resistant to antagonism by the 5‐HT 2 ‐receptor antagonist ketanserin and the 5‐HT3‐receptor antagonist MDL 72222 applied either microiontophoretically or administered systemically. 3 Microiontophoretic or systemic administration of the 5‐HT antagonist metergoline, which shows nanomolar affinity for the 5‐HT 1 ‐binding site, also failed to attenuate the depressant responses to 5‐HT. 4 Systemic administration of high doses of methysergide (30–40 mg kg −1 ) attenuated the depressant responses to 5‐HT but did not block depressant responses to GABA or excitatory responses to glutamate. 5 The depressant effects of 5‐HT were potently mimicked by the 5‐HT 1 ‐like receptor agonists 5‐carboxamidotryptamine and 8‐OH‐DPAT. 6 These results indicate that neither 5‐HT 2 ‐receptors nor 5‐HT 3 ‐receptors are involved in the depressant effects of 5‐HT on midline brainstem neurones. The depressant effects of 5‐carboxamidotryptamine (5‐CT) and 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) and blockade of the response to 5‐HT by high doses of methysergide suggests the involvement of 5‐HT 1 ‐like receptors. The lack of effect of metergoline, however, indicates that this receptor may be different from any of the 5‐HT 1 binding sites yet described.