Because ethanol has N-methyl-D-aspartate (NMDA) antagonist effects, we test
ed whether dizocilpine, an NMDA antagonist, reinstates ethanol-seeking beha
vior. Rats were trained to lever-press for a 10% ethanol/2% sucrose (EtOH)
or a 3% sucrose (Suc) solution using a two-lever tone lever active) procedu
re (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 gro
up showed minimal responding. Thus, ethanol reinstated ethanol-seeking beha
vior in a specific manner. In contrast, dizocilpine (0.175 mg/kg) increased
responding on both levers in both groups suggesting a loss of discriminati
ve control. Dizocilpine fails to reinstate ethanol-seeking behavior. These
data also demonstrate the necessity of using a discriminative, two-lever te
st for drug reinstatement. (C) 2001 Elsevier Science Inc. All rights reserv
ed.