Coordinating center (COC) management of pre-randomization eligibility in the diabetes control and complications trial (DCCT)

Abstract

It has been presumed that the combination of cocaine (COC)+heroin (HER) is more reinforcing than either of the two drugs alone, thus leading to their coadministration (“speedballing”). An alternative hypothesis is that HER serves to attenuate the undesired negative effects of COC. To test this notion, male Sprague–Dawley rats (n=31) were trained to run a straight alley for a daily intravenous (IV) injection of COC (1.0 mg/kg/injection) for 14 trials. Studies in our laboratory have shown that such animals begin to exhibit approach–avoidance behaviors (“retreats”) stemming from concurrent positive and negative associations with the goal box (which, in turn, are the result of COC's immediate rewarding and subsequent dysphoric actions). Thus, retreats can be used as a reliable index of COC's anxiogenic side effects. Following 14 COC-reinforced trials, animals were split into three groups matched on mean retreat frequency. One group (n=11) received IV COC (1.0 mg/kg/injection) for seven additional trials; the remaining two groups (n=10 each) received an IV injection of COC mixed in a single solution with either a low dose (0.025 mg/kg/injection) or a high dose (0.1 mg/kg/injection) of HER. It was hypothesized that adding HER would attenuate the negative consequences of COC administration and thereby produce a reliable decrease in the occurrence of retreats. The resulting data were consistent with this hypothesis, suggesting that “speedballing” in human addicts may be motivated by a desire to reduce the negative impact of COC use.