作者: Regina M. Carelli , Elizabeth A. West
DOI: 10.1016/J.NEUROPHARM.2013.04.025
关键词:
摘要: An important feature of cocaine addiction in humans is the emergence negative affect (e.g., dysphoria, irritability, anhedonia), postulated to play a key role craving and relapse. Indeed, DSM-IV recognizes that social, occupational and/or recreational activities become reduced as consequence repeated drug use where previously rewarding experiences food, job, family) devalued addict continues seek despite serious consequences. Here, research Carelli laboratory reviewed examined neurobiological mechanisms may underlie these processes using novel animal model. Oromotor responses (taste reactivity) were rats learned intraoral infusion sweet saccharin) predicts impending but delayed access self-administration. We showed exhibit aversive taste reactivity (i.e., gapes/rejection responses) during paired with cocaine, similar observed quinine, bitter tastant. Critically, expression this pronounced aversion predicted subsequent motivation self-administer cocaine. Electrophysiology studies show shift palatability corresponds an alteration nucleus accumbens (NAc) cell firing; neurons responded inhibition palatable shifted excitatory activity cocaine-devalued This response profile typically indicating once becomes following its association NAc encode state. also review electrochemical showing (from increase decrease) rapid dopamine release cocaine-paired tastant state developed, again, resulting quinine infusion. Collectively, our findings suggest cocaine-conditioned cues elicit cocaine-need aversive, encoded by distinct subset signaling, promotes cocaine-seeking behavior. Finally, we present data experimentally induced abstinence (30 days) exacerbates natural reward devaluation effect correlated greater lever press extinction. Dissecting neural underlying detrimental consequences critical since it lead treatments ameliorate affective states associated decrease drive (craving) for drug. article part Special Issue entitled 'NIDA 40th Anniversary Issue'.