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 properti es of heroin and the role of the opioid receptor activation in the ven tral tegmental area in heroin discrimination were examined. In Experim ent 1, male rats were trained to discriminate heroin (0.5 mg/kg, SC) f rom saline under conditions of exposure to restraint (15 min/day; thre e times a week) or no stress. Dose-response curves were subsequently d etermined 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 con trast, administration of restraint or the stress hormone corticosteron e just prior to drug injections decreased sensitivity to the heroin cu e. In Experiment 2, injections of morphine (5-10 mu g/side) into the v entral tegmental area (VTA, the cell body region of the mesocorticolim bic dopamine neurons) did not result in heroin-appropriate responding in animals trained to discriminate heroin injected systemically from s aline. Furthermore, intra-VTA injections of the opioid antagonist meth yl naltrexone (0.75-3.0 mu g/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 tempora l contiguity to the drug injection may reduce the sensitivity to the o pioid 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.