The combined effects of morphine and d-amphetamine on the threshold for brain stimulation reward

The effect of morphine and d-amphetamine co-administration on the threshold for rewarding intracranial electrical stimulation was studied in rats with electrodes stereotaxically implanted in the medial forebrain bundle-lateral hypothalamic or ventral tegmental area of the brain. Thresholds were determined by means of a rate-independent psychophysical method. Individually, morphine and d-amphetamine both caused a dose-related lowering of the reward threshold. Low doses of morphine or d-amphetamine which were ineffective or minimally effective in lowering the reward threshold were then tested with various doses of either d-amphetamine or morphine, respectively. In both cases, the combined administration of morphine and d-amphetamine resulted in a lowering of the reward threshold that was greater than for the corresponding doses of morphine and d-amphetamine when given alone. Given that increased sensitivity for rewarding brain stimulation has been suggested to be an animal model of drug-induced euphoria, this effect is congruent with the reported increase in the degree of euphoria produced when amphetamine is used in conjunction with opiate drugs.