Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.
The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, United States of America; Interdepartmental Program in Neuroscience, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
Andrew K
AK
Haack
Department of Pharmacology and Toxicology, University of Utah School of Medicine, United States Salt Lake City, Utah, United States of America.
Chandni
C
Sheth
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, United States of America; Interdepartmental Program in Neuroscience, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
Andrea L
AL
Schwager
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
Michael S
MS
Sinclair
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
Shashank
S
Tandon
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, United States of America; Interdepartmental Program in Neuroscience, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
Sharif A
SA
Taha
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000009:adverse effects / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D019262:Habenula / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D013651:Taste Disorders / Q000139:chemically induced / Q000503:physiopathology; D015016:Yohimbine / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D002492:Central Nervous System Depressants; D015016:Yohimbine; D000431:Ethanol