These studies addressed the question of serotonin (5-HT)-dopamine (DA) interactions with regard to reward-related behavior and motor activity in rats. The first experiment evaluated the effect of chronic treatment with fluoxetine (7 mg/kg/day), a serotonin-selective reuptake inhibitor, and buproprion (15 mg/kg/day), a dopamine reuptake inhibitor, on responding for conditioned reinforcement (CR). Chronic fluoxetine, but not buproprion, enhanced CR responding, and also potentiated cocaine-induced increases in CR responding. In the second experiment, animals received intra-accumbens infusions of either 1, 5, and 10 g) or DA (10, 20 g) The dopaminergic and serotonergic neurotransmitter systems are thought to play a critical role in the regulation of emotion and mood, and have been implicated in a spectrum of neuropsychiatric disorders. Psychotropic drugs affecting dopaminergic or serotonergic systems have been used to treat such disorders as depression, bipolar disorder, schizophrenia, eating disorders, obsessive compulsive disorder, and autism and have also been used to alleviate motor dysfunction associated with Tourette's syndrome, Parkinson's disease, and self-injurious behavior. Since both these transmitter systems appear to play such a critical role in mental functions, there has been a considerable amount of interest in their potential interactions. The nucleus accumbens, which has been implicated in reward and motivation, is one brain region where such an interaction may take place. There are high levels of dopamine (DA), dopamine receptors, serotonin (5-HT), and serotonin receptors in this forebrain region (Beal and Martin 1985;Bonaventure et al. 1997;Bouyer et al. 1984;Eberle-Wang et al. 1997;Joyce and Marshall 1987;Kilpatrick et al. 1987; Phelix and Broderick 1995;. The classical role of dopamine in the nucleus accumbens has been attributed to regulating motivation and reward-related behavior (Robbins and Everitt 1996;Schultz 1997;Wise and Rompré 1989). For example, drugs of abuse, such as cocaine and amphetamine, are believed to exert their euphoric effects primarily via activating the dopamine system (Di Chiara and Imperato 1988; Koob and Bloom 1988). In contrast to the substantial body of research on dopamine in the nucleus accumbens, there has been comparatively little attention given to the role of serotonin and serotonin-dopamine interactions in the nucleus accumbens.There are a number of reasons why further understanding of dopamine-serotonin interactions would be useful. Although depression undoubtedly involves a complex dysregulation of many transmitter and neuroendocrine systems, a majority of drugs used to treat depression affects the serotonin system. Serotoninselective re-uptake inhibitors (SSRIs) such as fluoxetine enhance synaptic levels of serotonin (5-HT), and are generally quite effective in ameliorating the symptoms of depression. Thus, one widely held hypothesis is that dysfunction in serotonergic neurons and their targets may underlie depressive symptomatology (van Praag et al. 1...