Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and...

Area of Science:

• Neuroscience
• Behavioral Science
• Addiction Research

Background:

• Environmental context plays a crucial role in modulating responses to cues.
• Understanding these contextual influences is vital for addressing substance use disorders, particularly alcohol use disorder.

Purpose of the Study:

• To investigate how an alcohol-associated context affects alcohol-seeking behavior triggered by conditioned stimuli.
• To elucidate the specific roles of mesolimbic dopamine circuits in context-dependent alcohol seeking.

Main Methods:

• Utilized an animal model to study alcohol-seeking behavior.
• Administered eticlopride and employed chemogenetics to inhibit ventral tegmental area (VTA) dopamine neurons.
• Examined the effects of VTA dopamine terminal silencing in the nucleus accumbens (NAc) core and shell.

Main Results:

• An alcohol-associated context elevated conditioned stimulus (CS)-triggered alcohol seeking.
• This contextual effect persisted across sessions and aided in reinstatement after extinction.
• Inhibition of VTA dopamine neurons reduced CS-triggered alcohol seeking.
• Silencing VTA dopamine terminals in the NAc core reduced seeking irrespective of context.
• Silencing VTA dopamine terminals in the NAc shell selectively reduced context-dependent alcohol seeking.

Conclusions:

• Divergent mesolimbic dopamine circuits have distinct roles in cue-driven alcohol seeking and its contextual amplification.
• The NAc shell is specifically involved in amplifying alcohol seeking within an alcohol-associated context.