Testosterone reinforcement: Intravenous and intracerebroventricular self-administration in male rats and hamsters

Rationale: Anabolic steroids are drugs of abuse. However, the potential for addiction remains unclear. Testosterone induces conditioned place preference in rats and oral self-administration in hamsters. Objectives: To determine if male rats and hamsters consume testosterone by intravenous (IV) or intracerebroventricular (ICV) self-administration. Methods: With each nose-poke in the active hole during daily 4-h tests in an operant conditioning chamber, gonad-intact adult rats and hamsters received 50 μg testosterone in an aqueous solution of β-cyclodextrin via jugular cannula. The inactive nose-poke hole served as a control. Additional hamsters received vehicle infusions. Results: Rats (n=7) expressed a significant preference for the active nose-poke hole (10.0±2.8 responses/4 h) over the inactive hole (4.7±1.2 responses/4 h). Similarly, during 16 days of testosterone self-administration IV, hamsters (n=9) averaged 11.7±2.9 responses/4 h and 6.3±1.1 responses/4 h in the active and inactive nose-poke holes, respectively. By contrast, vehicle controls (n=8) failed to develop a preference for the active nose-poke hole (6.5±0.5 and 6.4±0.3 responses/4 h). Hamsters (n=8) also self-administered 1 μg testosterone ICV (active hole:39.8±6.0 nose-pokes/ 4 h; inactive hole: 22.6±7.1 nose-pokes/4 h). When testosterone was replaced with vehicle, nose-poking in the active hole declined from 31.1±7.6 to 11.9±3.2 responses/ 4 h within 6 days. Likewise, reversing active and inactive holes increased nose-poking in the previously inactive hole from 9.1±1.9 to 25.6±5.4 responses/4 h. However, reducing the testosterone dose from 1 μg to 0.2 μg per 1 μl injection did not change nose-poking. Conclusions: Compared with other drugs of abuse, testosterone reinforcement is modest. Nonetheless, these data support the hypothesis that testosterone is reinforcing.