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 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-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 (ED50 = 1.5 micrograms/kg) was approximately 45 times more potent than ipsapirone, buspirone or 5-methoxy-N,N-dimethyltryptamine (ED50 range = 6.0-6.8 micrograms/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-HT1A 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-HT1A agonist compounds in unanesthetized animals and suggest that 5-HT1A 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.
Fornal
C A
CA
Department of Psychology, Princeton University, New Jersey.
Litto
W J
WJ
Metzler
C W
CW
Marrosu
F
F
Tada
K
K
Jacobs
B L
BL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D003864:Depression, Chemical; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011292:Premedication; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology
D065127:Dopamine D2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; D012701:Serotonin; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol