Pentobarbital-induced place preference in rats is blocked by GABA, dopamine, and opioid antagonists

Rationale: Drugs that are self-administered usually produce a conditioned place preference (CPP) but pentobarbital is self-administered by both animals and humans and is reported to be aversive in the CPP test. Objectives: We tested whether pentobarbital (5, 15, and 25 mg/kg; IP) could produce a place preference and examined the role of GABA, dopamine (DA) and opioid receptors in the pentobarbital CPP. Methods: Place conditioning was carried out in an apparatus consisting of two compartments connected by an alley at the rear. During the pre-exposure and test phase, the rats were free to wander in the apparatus for 20 min, and were drug-free. During the 6-day conditioning phase, rats were injected with drug (or vehicle), and confined to one compartment for 30 min and on alternate days were injected with vehicle (or drug) and confined to the other compartment. Upon obtaining a CPP, we examined whether pretreatment of the GABA(A) antagonists picrotoxin or bicuculline (0.5, 1.0, and 2.0 mg/kg; IP), the DA antagonist eticlopride (0.01, 0.05, and 0.25 mg/kg; SQ, or the opioid antagonist naloxone (0.02, 0.20, and 2.0 mg/kg; IP) would block the CPP. Results: 15 mg/kg pentobarbital produced a CPP. The pentobarbital CPP was blocked by pretreatment of 1.0 and 2.0 mg/kg bicuculline, but not by 0.5, 1.0, or 2.0 mg/kg picrotoxin. The pentobarbital CPP was also blocked by 0.05 and 0.25 mg/kg eticlopride and by all of the doses of naloxone tested. Conclusions: Pretreatment with the antagonists bicuculline, eticlopride, and naloxone blocked a 15 mg/kg pentobarbital CPP. This indicates that GABAergic, dopaminergic, and opioid systems play a role in the reinforcing properties of pentobarbital.