Abstract
Dynorphin (DYN), and its receptor, the kappa opioid receptor (KOR) are involved in drug seeking and relapse but the mechanisms are poorly understood. One hypothesis is that DYN/KOR activation promotes drug seeking through increased impulsivity, because many stimuli that induce DYN release increase impulsivity. Here, we systematically compare the effects of drugs that activate DYN/KOR on performance on the 5-choice serial reaction time task (5-CSRTT), a test of sustained attention and impulsivity. In Experiment 1, we determined the effects of U50,488 (0, 2.5, 5 mg/kg), yohimbine (0, 1.25, 2.5 mg/kg), and nicotine (0, 0.15, 0.3 mg/kg) on 5-CSRTT performance. In Experiment 2, we determined the effects of alcohol (0, 0.5, 1.0, 1.5 g/kg) on 5-CSRTT performance before and after voluntary, intermittent alcohol exposure. In Experiment 3, we determined the potential role of KOR in the pro-impulsive effects of yohimbine (1.25 mg/kg) and nicotine (0.3 mg/kg) by the prior administration of the KOR antagonist nor-BNI (10 mg/kg). Premature responding, the primary measure of impulsivity, was reduced by U50,488 and alcohol, but these drugs had a general suppressive effect. Yohimbine and nicotine increased premature responding. Yohimbine-, but not nicotine-induced increases in premature responding were blocked by nor-BNI, suggesting that impulsivity induced by yohimbine is KOR dependent. This may suggests a potential role for KOR-mediated increases in impulsivity in yohimbine-induced reinstatement.