Evidence for depressant 5-HT1-like receptors on rat brainstem neurones.
1. The technique of microiontophoresis was used to evaluate the contribution of 5-HT1-like, 5-HT2- and 5-HT3-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-HT2-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-HT1-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-HT1-like receptor agonists 5-carboxamidotryptamine and 8-OH-DPAT. 6. These results indicate that neither 5-HT2-receptors nor 5-HT3-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-HT1-like receptors. The lack of effect of metergoline, however, indicates that this receptor may be different from any of the 5-HT1 binding sites yet described.
Davies
M
M
Department of Physiology, University College Cardiff.
Wilkinson
L S
LS
Roberts
M H
MH
D000818:Animals; D001933:Brain Stem / Q000032:analysis* / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008711:Metergoline / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009474:Neurons / Q000032:analysis* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000032:analysis* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D008711:Metergoline; D007650:Ketanserin; C042253:bemesetron; D008784:Methysergide