Motivational alterations in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry and the nucleus accumbens. In the present study, the HIV-1 transgenic (Tg) rat was used to assess long-term HIV-1 viral protein exposure on motivated behavior using activity chambers (40x40cm) and voluntary wheel running. Adult ovariectomized female HIV-1 Tg animals (n=21) to F344 controls (n=26) were pair-housed under a 12:12 light/dark cycle. Voluntary running was measured with 34 cm-diameter running wheels for ~60 minutes/day for 3 ½ months. There were no significant differences between HIV-1 Tg and F344 control rats in voluntary wheel running during the light phase. Animals were subsequently run in the nocturnal phase of their light/dark cycle. The F344 controls continued to escalate their overall running distances and surpassed the stabilized HIV-1 Tg group after ~4 weeks of nocturnal running, until reaching their asymptotic plateau at week 11. Neither maximal running speed, nor the latency to initiate running or running bout length were significantly different between groups. However, the groups were different in the number of running bouts per session, as a function of the HIV-1 transgene. Collectively, the selective alterations in the motivation for voluntary wheel running and activity chamber locomotor activity, suggests a disruption of the motivational circuitry within the HIV-1 Tg rat brain. Examination of Medium Spiny Neurons of the nucleus accumbens showed significant alterations in dendritic spine length and spine head diameter. Further study of these alterations in spine parameters may help elucidate the mechanisms of motivational alterations in HIV-1+individuals