Opposing Roles of Rapid Dopamine Signaling Across the Rostral–Caudal Axis of the Nucleus Accumbens Shell in Drug-Induced Negative Affect
| Autor: | Regina M. Carelli, Seth W. Hurley, Elizabeth A. West |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Drug Taste Light Tyrosine 3-Monooxygenase Dopamine media_common.quotation_subject Self Administration Nucleus accumbens Affect (psychology) Nucleus Accumbens Article 03 medical and health sciences Self Stimulation 0302 clinical medicine Channelrhodopsins Cocaine Dopamine Uptake Inhibitors Reward Avoidance Learning medicine Animals Rats Long-Evans Biological Psychiatry media_common Addiction Ventral Tegmental Area Rats Ventral tegmental area 030104 developmental biology medicine.anatomical_structure Dopaminergic pathways Cues Rats Transgenic Psychology Reinforcement Psychology Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Biological Psychiatry. 82:839-846 |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2017.05.009 |
| Popis: | Background Negative reinforcement theories of drug addiction posit that addicts use drugs to alleviate negative mood states. In a preclinical model developed in our laboratory, rats exhibit negative affect to a normally rewarding taste cue when it predicts impending but delayed cocaine. The emergence of this state is accompanied by a reduction in dopamine concentration in the rostral nucleus accumbens (NAc) shell. However, the rostral and caudal regions of the shell have been implicated in promoting opposing appetitive and aversive states, respectively. Here, we tested whether dopamine transmission along the rostral-caudal axis of the shell plays differential roles in the emergence of drug-induced negative affect. Methods In TH::Cre rats, the dopaminergic pathways from the ventral tegmental area to the rostral and caudal regions of the shell were optogenetically stimulated during intraoral delivery of a taste cue signaling delayed cocaine. Affective responses to the taste cue were measured using taste-reactivity, and optical self-stimulation of the rostral and caudal shell was also examined. Results Optical stimulation of the rostral shell during tastant infusion prevented the emergence of negative affect, but activation of the caudal shell exacerbated aversive responses. These effects endured in the absence of optical stimulation, and the degree of negative affect in our model predicted self-stimulation responding. Conclusions These findings reveal unprecedented, pronounced and opposing roles of rapid dopamine signaling across the rostral-caudal axis of the NAc in the control of drug-induced negative affect, a hallmark of continued drug seeking and use in human addicts. |
| Databáze: | OpenAIRE |
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