Reinstatement of Alcohol Reinforcement

Protracted Abstinence

Behavioral procedures have been developed to reinstate alcohol seeking after extinction. Previously neutral stimuli, such as a tone, light, or odor, that are paired with alcohol self-administration or predict alcohol self-administration can induce relapse. Rats can come to associate a specific olfactory stimulus with alcohol availability, and that olfactory stimulus can then reinstate responding in animals subjected to extinction. Consistent with the well-established conditioned cue reactivity in human individuals with alcoholism, the motivational effects of alcohol-related stimuli are highly resistant to extinction and retain their efficacy to elicit alcohol-seeking behavior over more than 1 month of repeated testing. Such reinstatement can be blocked by systemic administration of naltrexone and selective μ and δ opioid receptor antagonists. Dopamine D1 and D2 receptor antagonists also block cue-induced reinstatement. Stress exposure can reinstate responding for alcohol in previously extinguished rats, and this stress-induced reinstatement is blocked by CRF antagonists. CRF antagonists block stress-induced reinstatement but not cue-induced reinstatement, and naltrexone blocks cue-induced reinstatement but not stress-induced reinstatement, suggesting two independent neuropharmacological routes to reinstatement and relapse (for further reading, see Liu and Weiss, 2002; Table 6.10).


Stress and Anti-Stress Neurotransmitters Implicated in the Motivational Effects of Alcohol Dependence and Withdrawal

Increased Activity

Decreased Activity

_ Corticotropin-releasing factor

_ Neuropeptide Y

_ Norepinephrine

_ Nociceptin (orphanin FQ)

_ Vasopressin

_ Endocannabinoids

_ Orexin (hypocretin)


_ Dynorphin


_ Substance P


Back to top