The pharmacological stressor yohimbine, but not U50,488, increases responding for conditioned reinforcers paired with ethanol or sucrose.

Abstract

Environmental stimuli paired with alcohol can function as conditioned reinforcers (CRfs) and trigger relapse to alcohol-seeking. In animal models, pharmacological stressors can enhance alcohol consumption and reinstate alcohol-seeking, but it is unknown whether stress can potentiate the conditioned reinforcing properties of alcohol-paired stimuli. We examined whether the pharmacological stressors, the α-2 adrenoreceptor antagonist yohimbine (vehicle, 1.25, 2.5 mg/kg; IP) and the K-opioid receptor agonist U50,488 (vehicle, 1.25, 2.5 mg/kg; SC), increase responding for conditioned reinforcement, and if their effects interact with the nature of the reward (alcohol vs. sucrose). We subsequently examined the effects of yohimbine (vehicle, 1.25, 2.5 mg/kg; IP) on responding for sensory reinforcement. Male Long-Evans underwent Pavlovian conditioning, wherein a tone-light conditioned stimulus (CS) was repeatedly paired with 12% EtOH or 21.7% sucrose. Next, tests of responding for a CRf were conducted. Responding on the CRf lever delivered the CS, whereas responding on the other lever had no consequences. In a separate cohort of rats, the effects of yohimbine on responding just for the sensory reinforcer were examined. Both doses of yohimbine, but not U50,488, increased responding for conditioned reinforcement. This enhancement occurred independently of the nature of the reward used during Pavlovian conditioning. Yohimbine-enhanced responding for a CRf was reproducible and stable over five tests; it even persisted when the CS was omitted. Both doses of yohimbine also increased responding for sensory reinforcement. Yohimbine increases operant responding for a variety of sensory and conditioned reinforcers. This enhancement may be independent of its stress-like effects.