Effect of σ1 receptor antagonism on ethanol and natural reward seeking

sigma(1) Receptors have been implicated in cognitive function, anxiety, depression, and the regulation of stress responses. In addition, sigma(1) receptors have been shown to participate in the behavioral and motivational effects of psychostimulants. Recent studies have shown that sigma(1) receptor antagonism prevents ethanol-induced conditioned place preference in mice and excessive drinking in alcohol-dependent or alcohol-preferring rats. Therefore, this study was designed to determine whether this role for sigma(1) receptors extends to ethanol-seeking behavior using an animal model of relapse and tested whether the suppressant effect of a potent sigma(1) receptor antagonist, BD1047, generalizes to natural reward-seeking behavior. Two separate groups of rats were trained to orally self-administer 10% (w/v) ethanol or a highly palatable reinforcer, 3%/0.125% (w/v) glucose/saccharin (SuperSac), in the presence of a discriminative stimulus (S+). Following extinction, during which the reinforcers and S+ were withheld, the presentation of the ethanol or SuperSac S+ produced comparable recovery of responding. BD1047 (1-20 mg/kg) exerted similar behavioral effects on both ethanol S+-induced and SuperSac S+-induced reinstatement, with the prevention of conditioned reinstatement only at the highest BD1047 dose. The present results show that sigma(1) receptor blockade under the present conditions exerts similar effects on conditioned reinstatement induced by ethanol-related and SuperSac-related stimuli, suggestive of overlapping neural mechanisms that control ethanol and natural reward seeking. NeuroReport 23:809-813 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.