TY - JOUR
T1 - Single-unit responses of serotonergic dorsal raphe neurons to 5-HT(1A) agonist and antagonist drug administration in behaving cats
AU - Fornal, C. A.
AU - Litto, W. J.
AU - Metzler, C. W.
AU - Marrosu, F.
AU - Tada, K.
AU - Jacobs, B. L.
PY - 1994
Y1 - 1994
N2 - Single-unit activity of serotonergic neurons in the dorsal raphe nucleus was recorded in free-moving cats in response to i.v. administration of 5- hydroxytryptamine (5-HT)(1A) agonist and antagonist drugs. The 5-HT(1A) 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 (ED50 = 1.5 μg/kg) was approximately 4 times more potent than ipsapirone, buspirone or 5- methoxy-N,N-dimethyltryptamine (ED50 range = 6.0-6.8 μg/kg) in producing inhibition, and all drugs were more effective when cats were inactive (e.g., drowsiness) than during periods of behavioral arousal (e.g., active waking). Administration of the 5-HT(1A) autoreceptor antagonist spiperone (0.25 and 1 mg/kg) produced a rapid, dose-dependent increase in the firing rate, suggesting that under physiological conditions serotonergic neurons are controlled by tonic feedback inhibition. This effect was evident during wakefulness (a period of relatively high neuronal activity), but not during sleep (a period of relatively low neuronal activity). Spiperone also blocked the inhibitory action of 8-OH-DPAT in a dose- and time-dependent manner. There was a strong positive correlation between the magnitude of spiperone- induced neuronal activation and blockade of 8-OH-DPAT-induced neuronal suppression. These effects of spiperone cannot be attributed to its dopaminergic D2 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 results confirm the marked sensitivity of serotonergic dorsal raphe nucleus neurons to selective 5-HT(1A) agonist compounds in unanesthetized animals and suggest that 5- HT(1A) somatodendritic autoreceptors exert a tonic inhibitory influence on the firing rate of these neurons during periods of behavioral activation, but not during periods of behavioral quiescence.
AB - Single-unit activity of serotonergic neurons in the dorsal raphe nucleus was recorded in free-moving cats in response to i.v. administration of 5- hydroxytryptamine (5-HT)(1A) agonist and antagonist drugs. The 5-HT(1A) 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 (ED50 = 1.5 μg/kg) was approximately 4 times more potent than ipsapirone, buspirone or 5- methoxy-N,N-dimethyltryptamine (ED50 range = 6.0-6.8 μg/kg) in producing inhibition, and all drugs were more effective when cats were inactive (e.g., drowsiness) than during periods of behavioral arousal (e.g., active waking). Administration of the 5-HT(1A) autoreceptor antagonist spiperone (0.25 and 1 mg/kg) produced a rapid, dose-dependent increase in the firing rate, suggesting that under physiological conditions serotonergic neurons are controlled by tonic feedback inhibition. This effect was evident during wakefulness (a period of relatively high neuronal activity), but not during sleep (a period of relatively low neuronal activity). Spiperone also blocked the inhibitory action of 8-OH-DPAT in a dose- and time-dependent manner. There was a strong positive correlation between the magnitude of spiperone- induced neuronal activation and blockade of 8-OH-DPAT-induced neuronal suppression. These effects of spiperone cannot be attributed to its dopaminergic D2 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 results confirm the marked sensitivity of serotonergic dorsal raphe nucleus neurons to selective 5-HT(1A) agonist compounds in unanesthetized animals and suggest that 5- HT(1A) somatodendritic autoreceptors exert a tonic inhibitory influence on the firing rate of these neurons during periods of behavioral activation, but not during periods of behavioral quiescence.
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M3 - Article
C2 - 7932189
AN - SCOPUS:0028030278
SN - 0022-3565
VL - 270
SP - 1345
EP - 1358
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -