Modeling Relapse to Pavlovian Alcohol-Seeking in Rats Using Reinstatement and Spontaneous Recovery Paradigms

Abstract

Background: Animal models are critical for studying causal explanations of relapse. Using a Pavlovian conditioning procedure with alcohol, we examined relapse after extinction triggered by either re-exposure to alcohol (reinstatement) or a delay between extinction and test (spontaneous recovery).

Methods: Male, Long-Evans rats were acclimated to 15% alcohol in the home-cage using an intermittent-access 2-bottle choice procedure. Next, they received Pavlovian conditioning sessions in which an auditory-conditioned stimulus (CS; 20 second white noise; 8 trials/session; variable time 240 seconds) was paired with 15% alcohol (0.3 ml/CS; 2.4 ml/session) that was delivered into a fluid port for oral ingestion. In subsequent extinction and test sessions, CS presentations occurred as before, but without alcohol.

Results: In experiment 1, exposure to either alcohol or water in the fluid port following extinction reinstated CS-elicited port entries at test 24 hours later. In a follow-up study using the same procedure (experiment 2), reinstatement was more robustly stimulated by alcohol, compared to a familiar lemon-flavored liquid. In experiment 3, systemic alcohol injections (0, 0.5, or 1.0 g/kg, intraperitoneal) administered either 24 hours or 15 minutes before test did not reinstate CS-elicited alcohol-seeking. Importantly, enzymatic assays in experiment 4 revealed detectable levels of alcohol in the blood following oral alcohol intake or intraperitoneal injection, suggesting that a pharmacological effect was likely with either route of administration. Last, in experiment 5, a 23-day delay between extinction and test resulted in a robust spontaneous recovery of CS-elicited alcohol-seeking.

Conclusions: The reinstatement and spontaneous recovery effects revealed herein provide evidence of viable new behavioral paradigms for testing interventions against relapse.

Keywords: Alcohol Use Disorders; Ethanol; Goal Tracking; Pavlovian-Conditioned Approach; Priming.