Testosterone as a discriminative stimulus in male rats.

Testosterone and other anabolic-androgenic steroids (AAS) are reinforcing in animals, as determined by conditioned place preference or self-administration. Most drugs of abuse produce subjective effects on mood and perception that initiate and maintain drug taking. Whether AAS have similar effects is not known. Food-restricted male Sprague-Dawley rats (n=9) were tested for their ability to discriminate an injection of testosterone from the β-cyclodextrin vehicle using a standard two-lever operant paradigm. In drug discrimination, animals use the subjective effects of drug or vehicle to select the appropriate lever to obtain food pellets under an FR10 schedule of reinforcement. All rats demonstrated vigorous responding for food (1415.1±76.1 responses/20 min) with 94.9% of responses on the active lever. For the first 30 days, rats received 1mg/kg testosterone sc 30 min before testing. On Day 14, one rat achieved the discrimination criteria of 9/10 consecutive days with >90% responses on the active lever and ≤5 responses on the inactive lever before the first reinforcement. Subsequently, rats were tested with testosterone at different doses (2, 7.5, 15 mg/kg at 30 min before testing) and times (2mg/kg at 30 or 60 min before testing), each for 20 days. One additional rat demonstrated successful discrimination at Day 54 with 2mg/kg testosterone 60 min before testing. The remaining 7 rats failed to discriminate testosterone within 110 days. When analyzed according to less-stringent standards, 4 additional rats met criteria for testosterone discrimination. However, continued performance was not stable. Thus, testosterone was unable to consistently support drug discrimination. We conclude that testosterone does not produce rapid interoceptive effects (NIH DA12843 to RIW).