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Nicotinic acetylcholine receptors in the ventral tegmental area mediate the dopamine activating and reinforcing properties of ethanol cues
- Source :
- Psychopharmacology. 195(3)
- Publication Year :
- 2007
-
Abstract
- Cues associated with alcohol can elicit craving, support drug-seeking and precipitate relapse.We investigated the possible involvement of nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) in the conditioned reinforcing properties of ethanol-associated stimuli in the rat.First, using in vivo microdialysis, we analyzed the effect of VTA perfusion of the nonselective nAChR antagonist mecamylamine (MEC) or the selective alpha4beta2* nAChR antagonist dihydro-beta-erythroidine (DHbetaE) on the nucleus accumbens (nAc) dopaminergic response to the presentation of an ethanol-associated conditioned stimulus (CS). Second, rats were trained to associate a tone+light CS with the presentation of 10% ethanol and were subsequently tested on the acquisition of a new instrumental response with conditioned reinforcement (CR) after local VTA infusion of MEC, DHbetaE, or alpha-Conotoxin MII (alpha-CtxMII, a selective alpha3beta2* and alpha6* nAChR antagonist).The ethanol-associated CS elevated nAc dopamine, an effect that was blocked by VTA perfusion of MEC but not DHbetaE. Systemic administration of MEC or local VTA infusion of MEC or alpha-CtxMII selectively blocked ethanol-associated CR, whereas systemic DHbetaE had no effect.We hypothesize a novel mechanism by which alcohol-associated cues promote drug-seeking behavior via activation of dopamine-stimulating alpha-CtxMII-sensitive nAChRs in the VTA. Pharmacological manipulations of selective nAChRs may thus be possible treatment strategies to prevent cue-induced relapse.
- Subjects :
- Male
Dopamine
Microdialysis
Self Administration
Nicotinic Antagonists
Pharmacology
Nucleus accumbens
Mecamylamine
Receptors, Nicotinic
Rats, Sprague-Dawley
mental disorders
medicine
Animals
Nicotinic Agonists
Nicotinic Antagonist
Rats, Wistar
Ethanol
Chemistry
musculoskeletal, neural, and ocular physiology
Dopaminergic
Ventral Tegmental Area
Dihydro-beta-Erythroidine
Rats
Ventral tegmental area
medicine.anatomical_structure
Nicotinic agonist
nervous system
Conditioning, Operant
Cues
Conotoxins
Neuroscience
Reinforcement, Psychology
Acetylcholine
medicine.drug
Subjects
Details
- ISSN :
- 00333158
- Volume :
- 195
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....f57c79efc3d018cfbe1e87ab4dd60641