Morphine-associated environmental cues elicit conditioned gene expression

Drug-associated contextual cues can exert a powerful influence on behavior through associative pairing between the drug and the environment. However, the anatomical and molecular substrates far these effects are not well char acterized. Using a drug-conditioning paradigm, we examined the expression o f the immediate early gene product, Fos. within specific brain circuits usi ng immunocytochemical detection. Rats were given either morphine (5 mg/ml/k g) or saline once a day for 10 days. The drug administration was always pai red with a specific environment (activity monitors) different from the home cage. Following this treatment, the rats were returned to the cages at var ious times thereafter, with only a mock injection. Conditioned behavioral a ctivation was observed in rats at 3, 5, and 7 days following treatment with morphine. In rats showing the conditioned motor response, several cortical and limbic areas showed substantial increases in the number of Fos positiv e cells, indicating that these regions were more active during exposure to the drug-paired environment. Areas that were most activated included prefro ntal cortex, cingulate cortex, nucleus accumbens, and preoptic area. Furthe r analysis showed that this increase in Fos expression was not directly rel ated to the increase in motor activity, and that the drug-associated condit ioning and Fos expression was lessened at 7 days and absent by 14 days post -treatment. These results are discussed in terms of their relevance to the problem of relapse in drug addiction. Synapse 37:146-158, 2000. (C) 2000 Wi ley-Liss, Inc.