Reinforcing effects of the neurosteroid allopregnanolone in rats

The GABA(A) receptor positive modulator allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) is a potent neurosteroid with behavioral and biochemical characteristics similar to ethanol, barbiturates, and benzodiazepines. This suggests that neurosteroids may provide an alternative class of sedative/hypnotic, anticonvulsant, and anxiolytic pharmacotherapies. However, there is evidence from animal models that neurosteroids may be susceptible to abuse by humans. Thus, the present study evaluated the reinforcing effects of orally administered allopregnanolone in rats. In the first experiment, male Long-Evans rats (n=9) were allowed to voluntarily consume a 50-microg/ml allopregnanolone (50A) solution or water in an unlimited-access two-bottle choice procedure for 10 days. Subsequently, the same animals were trained to lever-press to receive a 50A solution in daily 30-min operant sessions using a sucrose substitution procedure. In the two-bottle choice procedure, rats consumed significantly more allopregnanolone than water, suggesting that allopregnanolone was serving as a reinforcer. In the operant self-administration procedure, allopregnanolone did not maintain levels of responding that were different from water, suggesting that allopregnanolone did not function as a reinforcer in this procedure. These results suggest that orally administered allopregnanolone possesses reinforcing properties; however, additional studies are necessary to determine whether operant oral self-administration will be a viable index of allopregnanolone's reinforcing effects.