Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 38, Issue 5, Pages 2751-2761Publisher
WILEY
DOI: 10.1111/ejn.12278
Keywords
addiction; ethanol; nucleus accumbens; pavlovian conditioning; reinstatement; relapse
Categories
Funding
- National Institute of Alcohol Abuse and Alcoholism [RO1 AA014925]
- Fonds de la recherche en sante Quebec
- FRQS
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Environmental contexts associated with drug use promote craving in humans and drug-seeking in animals. We hypothesized that the basolateral amygdala (BLA) itself as well as serial connectivity between the BLA and nucleus accumbens core (NAC core) were required for context-induced renewal of Pavlovian-conditioned alcohol-seeking. Male Long-Evans rats were trained to discriminate between two conditioned stimuli (CS): a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2mL/CS+, 3.2mL per session) and a CS- that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS- without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using a solution of GABA receptor agonists (0.1mm muscimol and 1.0mm baclofen; M/B; 0.3L per side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6g per side) or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context.
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