Effects of GABAA Modulators in Rats Responding Under A Differential Reinforcement of Low Rates (DRL) Schedule

Abstract

Little is known about the behavioral effects of neurosteroids in comparison to other drugs that modulate the GABAA receptor complex. The present study examined the effects of pregnanolone (1 – 10 mg/kg) and DHEA (32 – 240 mg/kg) in male rats responding under a DRL‐18 sec schedule of reinforcement. Lorazepam (0.01 – 3.2 mg/kg), ethanol (0.32 – 2.4 g/kg), pentobarbital (1.8 – 18 mg/kg), β‐CCM (0.32 – 5.6 mg/kg) and flumazenil (3.2 – 18 mg/kg) were tested for comparison, and pregnanolone was administered in combination with DHEA to determine if there were any antagonistic effects between these substances. Pregnanolone increased responding at intermediate doses and decreased responding at high doses similar to lorazepam, ethanol, and pentobarbital. All four drugs dose‐dependently decreased percent reinforced responding and shifted the response distribution curve downward and to the left. Dose‐effect curves were similar for DHEA, β‐CCM, and flumazenil, but different from those for the other four drugs (i.e., these drugs did not change response rate or shift the response distribution curve). DHEA did not antagonize the disruptive effects of pregnanolone on responding under this schedule. In summary, pregnanolone and DHEA produce effects on DRL responding similar to other drugs that modulate the GABAA receptor complex, and do not produce these effects through a single binding site. Supported by DA 019625