EFFECT OF THE PUTATIVE 5-HT1A ANTAGONISTS WAY100135 AND SDZ-216-525 ON 5-HT NEURONAL FIRING IN THE GUINEA-PIG DORSAL RAPHE NUCLEUS

The selective 5-hydroxytryptamine(1A) (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT, 0.5-35 mu g kg(-1) i.v.) produces a dose related reversible inhibition (ED(50) = 6.5 mu g kg(-1) i.v.) of the firing of serotonergic neurones in the dorsal raphe nucleus of the guinea-pig. Administration of N-tert-butyl-3(4-(2-methoxyphenyl)piperazine-1-yl)-2phenylpropanamide dihydrochloride (WAY100135, 0.5 mg kg(-1) i.v.), a specific 5-HT1A antagonist, antagonized the 8-OHDPAT induced inhibition of neuronal firing whilst methyl 4-{4-[4-(1,1,3-trioxo-2H-1,2-benzoisothiazol-2-yl)butyl]-1-piperazinyl}1H-indole-2-carboxylate (SDZ 216-525, 0.1-0.5 mg kg(-1) i.v.) (also a putative 5-HT1A antagonist) reduced the basal firing of 5-HT neurones and furthermore failed to antagonize the inhibition produced by 8-OHDPAT. These results indicate that WAY 100135 is a silent and selective 5-HT1A antagonist whereas SDZ 216-525 demonstrates a partial agonist activity at the somatodendritic 5-HT1A autoreceptor in the guinea-pig DRN.