Considerable evidence indicates that nucleus accumbens dopamine (DA) is involved in the regulation of instrumental response output, and that interference with DA transmission disrupts the ability of rats to overcome work-related response costs. The present experiments were conducted to assess the effects of accumbens DA depletions on the performance of variable interval schedules, to determine if the intermittence of a schedule, in itself, is an important determinant of sensitivity to accumbens DA depletions. For this purpose, two variable interval 30 s lever pressing schedules were used, each with different response requirements added to the interval requirement. For one of the schedules, the animals were reinforced for the first response after the interval elapsed (tandem variable interval/fixed ratio 1: VI/FR1). On the other schedule an additional work requirement was attached by requiring the rats to make five responses after the interval in order to receive reinforcement (tandem variable interval/fixed ratio 5: VI/FR5). Attachment of the additional work requirement led to greater response rates during baseline training. After training, rats were injected with either ascorbate vehicle or 6-hydroxydopamine (6-OHDA) into the nucleus accumbens. The effects of DA depletion on responding were highly schedule-dependent. DA depletions had no significant effect on lever pressing under the condition with low response requirement (VI/FR1), but these depletions substantially disrupted responding on the schedule with the higher response requirement (VI/FR5). The disruption of responding on the schedule with the high response requirement showed recovery over the 4 weeks of post-surgical testing. In a second experiment, the effect of 6-OHDA on spontaneous locomotion in an open field was assessed. The DA-depleted animals had impairments in locomotion and rearing compared with the vehicle treated rats when tested 8 days after surgery, but not when tested 29 days after surgery, which demonstrates recovery of locomotor function after the accumbens DA depletions. The results of these experiments support the hypothesis that nucleus accumbens DA is involved in regulating behavioral activation. The lever pressing experiment indicates that depletions of DA in the accumbens interfere with the processes that enable rats to overcome behavioral constraints such as work-related response costs, and suggest that the intermittence of reinforcement per se is not the most critical factor in determining sensitivity to accumbens DA depletions.