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 withdrawal symptoms in rats, we have hypothesized that butorphanol has rewarding properties indicative of abuse potential. To test this hypothesis, the effects of equimolar doses of butorphanol tartrate (0.5-5.0 μg) and morphine sulfate (0.8-8.0 μg) were assessed in inbred Lewis male rats using the conditioned place preference (CPP) paradigm. Unilateral microinjections (1 μl/inj) of saline or opioids were made into the ventral tegmental area (VTA). Microinjections of saline to controls were associated with both sides of modified Skinner boxes, whereas opioid injections were associated only with the white chambers (less preferred side to the naive animals). Opioids were administered alternating with saline in the drug-treated animals on alternating days. During 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 significant preference over saline, only the higher doses of butorphanol (2.0–5.0 μg) produced significant conditioned place preference for the sides of the chambers associated with the drugs. These results suggest that, like morphine which is widely abused, butorphanol also has rewarding properties, and, therefore, further investigations regarding its abuse potential are necessary.