A critical role of nucleus accumbens dopamine D1-family receptors in renewal of alcohol seeking after punishment-imposed abstinence.
In humans, places or contexts previously associated with alcohol use often provoke relapse during abstinence. This phenomenon is modeled in laboratory animals using the ABA renewal procedure, in which extinction training in context (B) suppresses alcohol seeking, and renewal of this seeking occurs when the animal returns to the original training context (A). However, extinction training does not adequately capture the motivation for abstinence in human alcoholics who typically self-initiate abstinence in response to the negative consequences of excessive use. We recently developed a procedure to study renewal in laboratory rats after abstinence imposed by negative consequences (footshock punishment). The mechanisms of renewal of punished alcohol seeking are largely unknown. Here, we used the D1-family receptor antagonist SCH 23390 to examine the role of nucleus accumbens (NAc) shell and core dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We trained alcohol-preferring "P rats" to self-administer 20% alcohol in Context A and subsequently suppressed alcohol taking via response-contingent footshock punishment in Context B. We tested the effects of systemic, NAc shell, or NAc core injections of SCH 23390 on renewal of alcohol seeking after punishment-imposed abstinence. We found that both systemic and NAc shell and core injections of SCH 23390 decreased renewal of punished alcohol seeking. Our results demonstrate a critical role of NAc dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We discuss these results in reference to the brain mechanisms of renewal of alcohol seeking after extinction versus punishment.
Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse.
Nathan J
NJ
Marchant
Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse.
Konstantin
K
Kaganovsky
D019973:Alcohol-Related Disorders / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D004597:Electroshock; D000431:Ethanol / Q000008:administration & dosage; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D020022:Genetic Predisposition to Disease; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011678:Punishment; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012646:Self Administration
D001552:Benzazepines; D002492:Central Nervous System Depressants; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D000431:Ethanol; D004298:Dopamine