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

Abstract

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. To determine if male rats and hamsters consume testosterone by intravenous (IV) or intracerebroventricular (ICV) self-administration. 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 microg testosterone in an aqueous solution of beta-cyclodextrin via jugular cannula. The inactive nose-poke hole served as a control. Additional hamsters received vehicle infusions. 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 microg 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 microg to 0.2 microg per 1 microl injection did not change nose-poking. Compared with other drugs of abuse, testosterone reinforcement is modest. Nonetheless, these data support the hypothesis that testosterone is reinforcing.