Morphine-induced conditioned place preference and associated behavioural plasticity in HIV-1 transgenic rats.

The prevalence of morphine addiction in HIV-1 infected persons is higher than the healthy population. The mu-opioid receptor (MOR) which mediates the actions of morphine is shown to be up-regulated in the HIV-1 transgenic (HIV-1Tg) rat. In this study, we used the conditioned place preference (CPP) test to investigate if HIV-1Tg rats are more sensitive to the addictive properties of morphine compared to F344 control animals. Morphine-CPP was successfully established in the HIV-1Tg and F344 rats at the dose of 3.5 mg/kg. Interestingly, the animals that had morphine paired with one side of the two-chamber CPP apparatus (the white chamber) failed to show any decline in preference for the morphine-paired chamber after 17 to 20 days of extinction testing. An analysis of the change in preference that occurs within a session as a result of the habituation of exploratory behaviour suggested that morphine enhanced a natural preference for the white chamber. We suggest that the morphine CPP procedure may sometimes result in a behavioural plasticity that does not conform to the predictive learning model of classical conditioning and may reflect a form of associative learning known as evaluative conditioning. The animals that had morphine paired with the other chamber (the black chamber) showed extinction. Moreover greater resistance to extinction was observed in the HIV-1Tg rats. Following extinction the HIV-1Tg and F344 groups were each divided into two groups. One group was tested for reinstatement following a 1 mg/kg and 3.5 mg/kg morphine prime on 2 consecutive days, respectively. The second group was tested for reinstatement after exposure to foot shock. Reinstatement with drug-prime or with the foot shock stressor was not observed.