COMPARATIVE REWARDING PROPERTIES OF MORPHINE AND BUTORPHANOL

Because butorphanol (Stadol), a synthetic morphinan compound, has been demonstrated in our laboratories to produce physical dependence and w ithdrawal symptoms in rats, we have hypothesized that butorphanol has rewarding properties indicative of abuse potential. To test this hypot hesis, the effects of equimolar doses of butorphanol tartrate (0.5-5.0 mu g) and morphine sulfate (0.8-8.0 mu g) were assessed in inbred Lew is male rats using the conditioned place preference (CPP) paradigm. Un ilateral microinjections (1 mu l/inj) of saline or opioids were made i nto the ventral tegmental area (VTA). Microinjections of saline to con trols were associated with both sides of modified Skinner boxes, where as opioid injections were associated only with the white chambers (les s preferred side to the naive animals). Opioids were administered alte rnating with saline in the drug-treated animals on alternating days. D uring eight conditioning sessions the rats learned to associate light and dark sides of the Skinner boxes with microinjections of opioids or saline, respectively. Although all doses of morphine induced signific ant preference over saline, only the higher doses of butorphanol (2.0- 5.0 mu g) produced significant conditioned place preference for the si des of the chambers associated with the drugs. These results suggest t hat, like morphine which is widely abused, butorphanol also has reward ing properties, and, therefore, further investigations regarding its a buse potential are necessary.