Habenula lesions decrease the responsiveness of dorsal raphe serotonin neurons to cocaine.
The median and dorsal (MR and DR) raphe nuclei are the origin of serotonin (5-HT)-containing neurons that innervate the forebrain. Neurons originating in the medial and lateral habenula provide an extensive afferent input to the midbrain that could serve as a negative feedback circuit. The present study was undertaken to establish whether intact habenula nuclei are required to observe the depressant effects of cocaine on the neural activity of 5-HT somata in the DR. To this end, the spontaneous activity of DR 5-HT neurons was assessed in male rats that had previously received bilateral radiofrequency lesions of the habenula complex either 1-4 h (short term) or 7 days (long term) prior to extracellular recordings of single 5-HT neurons of the DR. In rats with short-term lesions, the inhibitory response to cocaine was significantly attenuated. The mean dose to inhibit activity by 50% (ID50) was increased from 0.68 mg/kg in controls to 2.5 mg/kg in lesioned rats. Short-term habenula lesions also significantly decreased the numbers (but not the firing rates) of 5-HT neurons encountered in the DR. In contrast, the dose-response to cocaine as well as the numbers and firing rates of 5-HT neurons found in rats with long-term habenula lesions did not differ from controls. These results suggest that the inhibitory effects of cocaine on DR 5-HT neuronal activity depend in part on the ability of cocaine to affect habenula control of raphe 5-HT function.
Paris
J M
JM
Department of Pharmacology and Toxicology, University Texas Medical Branch, Galveston 77555-1031.
Cunningham
K A
KA
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007275:Injections, Intravenous; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D013788:Thalamus / Q000502:physiology*
D012701:Serotonin; D003042:Cocaine