Orally self-administered cocaine in rhesus monkeys: transition from negative or neutral behavioral effects to positive reinforcing effects.

The establishment of orally delivered cocaine as a reinforcer was examined with nine rhesus monkeys. A 2% ethanol solution served as a reinforcer for all nine monkeys, for it maintained substantially higher response rates than did the concurrently available water vehicle. A test was initially conducted to determine whether cocaine would function as a reinforcer when substituted for 2% ethanol. When an intermediate cocaine concentration (0.2 mg/ml) was substituted for the ethanol solution, the drug maintained behavior at rates less than (seven monkeys), equal to (one monkey), or greater than (one monkey) those maintained by water. Thus, for eight of nine monkeys simple substitution of cocaine for ethanol was not sufficient to establish orally delivered cocaine as a reinforcer. In the next phase a stimulus-fading procedure was used. Blocks of training and testing sessions alternated. Across blocks of training sessions, increasing amounts of cocaine (0.0125, 0.025, 0.05, 0.1 mg/ml) were added to the 2% ethanol solution and subsequently the ethanol concentration was gradually decreased until only the 0.1 mg/ml cocaine solution remained; water was always concurrently available. Between each block of training sessions, a block of test sessions was inserted. Test sessions compared relative rates of responding maintained by two concurrently available drug solutions: (1) a solution containing the combination of ethanol and cocaine used in the prior training block and (2) a solution containing the same concentration of ethanol but with no cocaine. Thus, differences in rates of behavior maintained by the two solutions could be attributed to the presence of cocaine and the existence and degree of any such differences could be monitored at each step in the acquisition procedure. The outcome of the training procedure was that cocaine came to function as a reinforcer for six of the eight monkeys tested (the ninth monkey was not put through the fading procedure, having shown higher cocaine than vehicle rates during the initial substitution procedure). During the phase when ethanol was faded from the drug solution, differences between the combination cocaine-ethanol solution and the ethanol-only solution emerged: for the six monkeys that developed cocaine reinforced behavior, the combination solution maintained higher rates of responding than the ethanol solution alone. The opposite results were obtained with the remaining two monkeys. That cocaine had been established as a reinforcer was confirmed by persistent and orderly responding when dose and fixed-ratio size were subsequently varied.