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

Abstract

IntroductionAlcohol-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.MethodsWe 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 μg/kg).ResultsSCH23390 significantly decreased firing rates during the 60 s 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.ConclusionsThese 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.

Nutritional Contingency Reduces Alcohol Drinking by Altering Central Neurotransmitter Receptor Gene Expression in Rats

“…Dopamine (DA) mediates its activity via D1-like (D1 and D5) and D2-like (D2, D3, D4) receptors which are widely distributed in the CNS [30]. A recent study demonstrated that D1-like, but not D2-like receptor blockade, in the striatal region impaired alcohol-induced conditioned place preference [31] and reduced alcohol-seeking behavior by modulating the neuronal activation in response to alcohol-associated cues [32]. While the involvement of the D5 receptor in regulating alcohol drinking or reward is less clear, a study has shown that D5 receptors are present and depolarize both cholinergic and GABAergic striatal interneurons following activation by DA and thereby are capable of modulating striatal GABAergic medium spiny projection neurons activity [33].…”

Leucine-Rich Repeat Kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking

“…Pharmacological blockade of D1-like receptors in the DMS, but not D2R, attenuates alcohol consumption ( 22, 23, 25 ). Further, D1-like receptor antagonist impair alcohol-seeking in an operant task ( 26 ). Collectively, these findings point to an important role of D1R function and striatal D1-MSN activity in driving alcohol drinking.…”

Leucine-rich repeat kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking

“…Pharmacological blockade of D1-like receptors, but not D2-like receptors, attenuates alcohol consumption when delivered in the dorsomedial striatum [ 17 – 19 ]. Further, D1-like antagonists impair alcohol-seeking in an operant task [ 20 ]. Other evidence shows that alcohol exposure elicits functional and structural plasticity selectively in D1-MSNs.…”