Alcohol seeking in C57BL/6 mice induced by conditioned cues and contexts in the extinction-reinstatement model.
We have recently shown that the alcohol self-administration context can reinstate extinguished responding for alcohol when that extinction occurs in a different context [Burattini, C., Gill, T. M., Aicardi, G., & Janak, P. H. (2006)]. The ethanol self-administration context as a reinstatement cue: acute effects of naltrexone. Neuroscience, in press; Zironi, I., Burattini, C., Aicardi, G., & Janak, P. H. (2006). Context is a trigger for relapse to alcohol. Behav Brain Res 167, 150-155). Here, we test whether the C57BL/6 mice will also show context-induced reinstatement for alcohol, and whether presentation of an alcohol-associated cue will alter the observed responding. Male C57BL/6 mice were trained to lever press on a fixed ratio-3 schedule for a 10% ethanol solution in a context made distinctive using visual, tactile, and olfactory stimuli. Each ethanol delivery was paired with a compound tone-light stimulus. After training, extinction sessions were given in a distinct context, comprised of different visual, tactile, and olfactory stimuli; the compound cue and the alcohol were not available during these sessions. In Experiment 1, after response extinction, subjects were tested by placement into both the alcohol self-administration context and, on a subsequent test, by response-contingent presentation of the cue following placement into the alcohol self-administration context. In Experiment 2, after response extinction, subjects were tested in both of these conditions, with the addition of a test of the effects of response-contingent presentation of the cue in the extinction context. The results indicate that the alcohol self-administration context produces a mild increase in responding at the alcohol lever, and that presentation of the alcohol-associated cue in the alcohol context, but not the extinction context, strongly increases responding on the alcohol lever. These findings suggest that the power of an alcohol-associated cue can be modulated by the context. The observed effects of alcohol contexts and cues on alcohol-seeking behavior in the C57BL/6 mouse suggest that this reinstatement model may be useful for understanding the neurobiological and genetic mechanisms of relapse triggered by conditioned environmental stimuli.
Tsiang
Margaret T
MT
Ernest Gallo Research Center, Department of Neurology, University of California, San Francisco, Emeryville, CA 94608, USA.
Janak
Patricia H
PH
D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D003463:Cues; D000431:Ethanol / Q000008:administration & dosage; D005108:Extinction, Psychological / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010775:Photic Stimulation; D010812:Physical Stimulation; D012646:Self Administration; D012903:Smell; D014110:Touch
D000431:Ethanol