A discriminative two-lever test of dizocilpine's ability to reinstate ethanol-seeking behavior

Because ethanol has N-methyl-D-aspartate (NMDA) antagonist effects, we tested whether dizocilpine, an NMDA antagonist, reinstates ethanol-seeking behavior. Rats were trained to lever-press for a 10% ethanol/2% sucrose (EtOH) or a 3% sucrose (Suc) solution using a two-lever (one lever active) procedure (FR2). After extinction, rats were injected with ethanol (0.5 g/kg). The EtOH group emitted more active than inactive lever presses and the Suc group showed minimal responding. Thus, ethanol reinstated ethanol-seeking behavior in a specific manner. In contrast, dizocilpine (0.175 mg/kg) increased responding on both levers in both groups suggesting a loss of discriminative control. Dizocilpine fails to reinstate ethanol-seeking behavior. These data also demonstrate the necessity of using a discriminative, two-lever test for drug reinstatement.