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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Weiss, F. Ciccocioppo, R. Sanna, P. P. |
| Description | Author Affiliation: Ciccocioppo R ( Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.); |
| Abstract | The conditioning of cocaine's subjective actions with environmental stimuli may be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of learning factors in persistent addictive behavior as well as the neurobiological basis of this phenomenon, rats were trained to associate discriminative stimuli (S(D)) with the availability of i.v. cocaine vs. nonrewarding saline solution, and then placed on extinction conditions during which the i.v. solutions and S(D)s were withheld. The effects of reexposure to the S(D) on the recovery of responding at the previously cocaine-paired lever and on Fos protein expression then were determined in two groups. One group was tested immediately after extinction, whereas rats in the second group were confined to their home cages for an additional 4 months before testing. In both groups, the cocaine S(D), but not the non-reward S(D), elicited strong recovery of responding and increased Fos immunoreactivity in the basolateral amygdala and medial prefrontal cortex (areas Cg1/Cg3). The response reinstatement and Fos expression induced by the cocaine S(D) were both reversed by selective dopamine D(1) receptor antagonists. The undiminished efficacy of the cocaine S(D) to elicit drug-seeking behavior after 4 months of abstinence parallels the long-lasting nature of conditioned cue reactivity and cue-induced cocaine craving in humans, and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. Moreover, the results implicate D(1)-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala as substrates for cocaine-seeking behavior elicited by cocaine-predictive environmental stimuli. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 98 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2001-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Behavior, Animal Drug Effects Benzazepines Pharmacology Brain Cocaine-Related Disorders Physiopathology Cocaine Dopamine Antagonists Dopamine Uptake Inhibitors Receptors, Dopamine D1 Antagonists & Inhibitors Substance Withdrawal Syndrome Animals Metabolism Pathology Administration & Dosage Dose-Response Relationship, Drug Proto-Oncogene Proteins C-fos Biosynthesis Rats, Wistar Time Factors Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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