SINGLE-UNIT RESPONSES OF SEROTONERGIC DORSAL RAPHE NEURONS TO 5-HT1A AGONIST AND ANTAGONIST DRUG ADMINISTRATION IN BEHAVING CATS

Single-unit activity of serotonergic neurons in the dorsal raphe nucle us was recorded in free-moving cats in response to i.v. administration of 5-hydroxytryptamine (5-HT)(1A) agonist and antagonist drugs. The 5 -HT1A agonist drugs 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) , ipsapirone, buspirone and 5-methoxy-N, N-dimethyltryptamine produced a rapid, dose-dependent inhibition of neuronal activity. 8-OH-DPAT (E D(50) = 1.5 mu g/kg) was approximately 4 times more potent than ipsapi rone, buspirone or 5-methoxy-N,N-dimethyltryptamine (ED(50) range = 6. 0-6.8 mu g/kg) in producing inhibition, and all drugs were more effect ive when cats were inactive (e.g., drowsiness) than during periods of behavioral arousal (e.g., active waking). Administration of the 5-HT1A autoreceptor antagonist spiperone (0.25 and 1 mg/ kg) produced a rapi d, dose-dependent increase in the firing rate, suggesting that under p hysiological conditions serotonergic neurons are controlled by tonic f eedback inhibition. This effect was evident during wakefulness (a peri od of relatively high neuronal activity), but not during sleep (a peri od of relatively low neuronal activity). Spiperone also blocked the in hibitory action of 8-OH-DPAT in a dose- and time-dependent manner. The re was a strong positive correlation between the magnitude of spiperon e-induced neuronal activation and blockade of 8-OH-DPAT-induced neuron al suppression. These effects of spiperone cannot be attributed to its dopaminergic D-2 or serotonergic 5-HT2 antagonist properties, because administration of haloperidol and ritanserin produced no increase in neuronal activity and did not block the action of 8-OH-DPAT. These res ults confirm the marked sensitivity of serotonergic dorsal raphe nucle us neurons to selective 5-HT1A agonist compounds in unanesthetized ani mals and suggest that 5-HT1A somatodendritic autoreceptors exert a ton ic inhibitory influence on the firing rate of these neurons during per iods of behavioral activation, but not during periods of behavioral qu iescence.