摘要：SummaryDespite many years of work on dopaminergic mechanisms of alcohol addiction, much of the evidence remains mostly correlative in nature. Fortunately, recent technological advances have provided the opportunity to explore the causal role of alterations in neurotransmission within circuits involved in addictive behaviors. Here, we address this critical gap in our knowledge by integrating an optogenetic approach and an operant alcohol self-administration paradigm to assess directly how accumbal dopamine (DA) release dynamics influences the appetitive (seeking) component of alcohol-drinking behavior. We show that appetitive reward-seeking behavior in rats trained to self-administer alcohol can be shaped causally by ventral tegmental area-nucleus accumbens (VTA-NAc) DA neurotransmission. Our findings reveal that phasic patterns of DA release within this circuit enhance a discrete measure of alcohol seeking, whereas tonic patterns of stimulation inhibit this behavior. Moreover, we provide mechanistic evidence that tonic-phasic interplay within the VTA-NAc DA circuit underlies these seemingly paradoxical effects.Graphical AbstractDisplay OmittedHighlights•VTA-NAc DA transmission can bidirectionally modulate motivated behavior•Optogenetic increases in phasic DA release in the NAc enhance alcohol seeking•Optogenetic increases in tonic DA release in the NAc inhibit alcohol seeking•Phasic DA release can be decreased by the concurrent tonic activationAnimal Physiology; Neuroscience; Behavioral Neuroscience
