Effects of restraint stress and intra-ventral tegmental area injections of morphine and methyl naltrexone on the discriminative stimulus effects of heroin in the rat.

The effect of restraint stress on the discriminative stimulus properties of heroin and the role of the opioid receptor activation in the ventral tegmental area in heroin discrimination were examined. In Experiment 1, male rats were trained to discriminate heroin (0.5 mg/kg, SC) from saline under conditions of exposure to restraint (15 min/day; three times a week) or no stress. Dose-response curves were subsequently determined under conditions of no stress, restraint, corticosterone (3 mg/kg, IP), and saline. Exposure to restraint during training did not alter heroin discrimination under any of the conditions tested. In contrast, administration of restraint or the stress hormone corticosterone just prior to drug injections decreased sensitivity to the heroin cue. In Experiment 2, injections of morphine (5-10 micrograms/side) into the ventral tegmental area (VTA, the cell body region of the mesocorticolimbic dopamine neurons) did not result in heroin-appropriate responding in animals trained to discriminate heroin injected systemically from saline. Furthermore, intra-VTA injections of the opioid antagonist methyl naltrexone (0.75-3.0 micrograms/side) did not block the discriminability of heroin given systemically. These results indicate that exposure to restraint stress or the stress hormone corticosterone in close temporal contiguity to the drug injection may reduce the sensitivity to the opioid cue. In addition, under the condition of the present experiment activation of opioid receptors in the VTA does not appear to mimic the discriminative stimulus effects of systemically administered heroin.