Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.Accumulating evidence suggests that certain personality traits, including sensation (or novelty) seeking, impulsivity, and antisocial conduct disorder, may predispose humans to drug abuse and addiction (1-4). However, from studies of human drug addicts alone, it is difficult to determine whether comorbid impulsivity and cognitive dysfunction (5, 6) pre-

Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However, an important but unresolved issue is whether this forebrain structure also contributes to the consolidation of fundamental forms of appetitive learning acquired by Pavlovian associative processes. In addition, although dopaminergic and glutamatergic influences in the NAc have been implicated in instrumental learning, it is unclear whether similar mechanisms operate during Pavlovian conditioning. To evaluate these issues, the effects of posttraining intra-NAc infusions of D1, D2, and NMDA receptor antagonists, as well as D-amphetamine, were determined on Pavlovian autoshaping in rats, which assesses learning by discriminated approach behavior to a visual conditioned stimulus predictive of food reward. Intracerebral infusions were given either immediately after each conditioning session to disrupt early memory consolidation or after a delay of 24 h. Findings indicate that immediate, but not delayed, infusions of both D1 (SCH 23390) and NMDA (AP-5) receptor antagonists significantly impair learning on this task. By contrast, amphetamine and the D2 receptor antagonist sulpiride were without significant effect. These findings provide the most direct demonstration to date that D1 and NMDA receptors in the NAc contribute to, and are necessary for, the early consolidation of appetitive Pavlovian learning.consolidation ͉ dopamine ͉ learning ͉ autoshaping ͉ glutamate T he nucleus accumbens (NAc) is increasingly regarded as a key forebrain structure underlying appetitive learning and memory (1, 2), and there is widespread interest in understanding the involvement of NAc dopamine (DA) and glutamate in this process (3-7). Blockade of D1 and NMDA receptors in the NAc impairs the acquisition, but not the performance, of appetitive instrumental conditioning (4,8). Likewise, antagonism of NAc NMDA and DA receptors (9), as well as selective NAc DA depletion (10, 11), impairs Pavlovian conditioned behavior. However, because all of these studies manipulated NAc DA and glutamate function prior to conditioning, it is possible that several processes relevant to learning and memory were affected, including acquisition, consolidation, and retrieval. Posttraining manipulations define more precisely the nature of the learning deficit, in addition to avoiding possible confounding effects of nonspecific performance factors on learning (12). Indeed, a number of studies report significant effects on radial maze and water maze learning after posttraining systemic (13,14), intracaudate (15), and intra-NAc (3) administration of DA receptor agents. Furthermore, recent research indicates that early consolidation of instrumental learning requires new protein synthesis in the NAc (16).However, there have been remarkably few studies investigating the involvement of DA and glutamate in the consolidation of appetitive Pavlovian learning. Although posttraini...

These data, together with recent findings of attentional dysfunction during the withdrawal of intravenous self-administration of amphetamine, suggest that generically different drugs of abuse produce similar disturbances in visual attentional performance during the early withdrawal period.