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One symptom of depression is loss of motivation, which can be defined as responsiveness to response-eliciting stimuli and quantified as reward-related behavioral output. L.ong-term changes in reward-related behavior have been shown to follow early life stress. Most rodent studies investigating the effects of postnatal separation, an early stress, on reward-related behavior have used drug rewards and few have used natural rewards. Given that separation has been implicated in depression in humans, who may experience impaired motivation without drug experience, it is important to understand how separation affects motivation for natural reward. We hypothesized that neonatal isolation would slow the acquisition of and reduce levels of food-rewarded operant responding , a measure of motivation, in rats. Eight male LongEvans rats were individually isolated from dams and littermates for 1 hr on postnatal days 2 through 9 while the dam stayed with remaining pups. Seven male siblings were handled to the same extent but without the isolation. When tested as adults on a lever pressing task under fixed and progressive ratio schedules of food reward, isolated rats acquired the operant response significantly more slowly than handled siblings and showed significantly lower levels of responding under all schedules. These results indicate that early separation causes a reduction in motivation, which may be one mechanism of human depression.