Habenula lesions decrease the responsiveness of dorsal raphe serotonin neurons to cocaine

Joseph M. Paris, Kathryn A. Cunningham

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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 nuclie are required to observe the depressant effects of cocaine on the neural activity of 5-HT somata in te 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.

Original languageEnglish (US)
Pages (from-to)555-560
Number of pages6
JournalPharmacology, Biochemistry and Behavior
Issue number3
StatePublished - Nov 1994
Externally publishedYes


  • Cocaine
  • Dorsal raphe
  • Electrophysiology
  • Habenula
  • Rat
  • Serotonin (5-HT)
  • Single-unit recording

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


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