Dopamine D1 receptor blockade impairs alcohol seeking without reducing dorsal striatal activation to cues of alcohol availability

作者：Fanelli Rebecca R; Robinson Donita L^*

来源：Brain and Behavior, 2015, 5(2): e00305.

DOI：10.1002/brb3.305

• dopamine D1 receptor antagonist SCH23390
• dorsolateral striatum
• dorsomedial striatum
• extracellular electrophysiology
• RRID:nif-0000-31484
• RRID:nlx_153890
• RRID:nlx_157643
• RRID:nlx_158483
• RRID:nlx_158484
• RRID:nlx_158504

Introduction: Alcohol-associated cues activate both ventral and dorsal striatum in functional brain imaging studies of heavy drinkers. In rodents, alcohol-associated cues induce changes in neuronal firing frequencies and increase dopamine release in ventral striatum, but the impact of alcohol-associated cues on neuronal activity in dorsal striatum is unclear. We previously reported phasic changes in action potential frequency in the dorsomedial and dorsolateral striatum after cues that signaled alcohol availability, prompting approach behavior. Methods: We investigated the hypothesis that dopamine transmission modulates these phasic firing changes. Rats were trained to self-administer alcohol, and neuronal activity was monitored with extracellular electrophysiology during "anticipatory" cues that signaled the start of the operant session. Sessions were preceded by systemic administration of the D1-type dopamine receptor antagonist SCH23390 (0, 10, and 20 mu g/kg). Results: SCH23390 significantly decreased firing rates during the 60s prior to cue onset without reducing phasic excitations immediately following the cues. While neuronal activation to cues might be expected to initiate behavioral responses, in this study alcohol seeking was reduced despite the presence of dorsal striatal excitations to alcohol cues. Conclusions: These data suggest that D1 receptor antagonism reduces basal firing rates in the dorsal striatum and modulates the ability of neuronal activation to "anticipatory" cues to initiate alcohol seeking in rats with an extensive history of alcohol self-administration.

• 出版日期2015-2