To better characterize the central nervous system response to peripheral insulin administration, male Sprague-Dawley rats were fitted with microdialysis probes in the nucleus accumbens (NAC; n = 23) and striatum (STR; n = 22). Awake intact rats were injected with either 0, 200, 400, or 600 mU regular insulin i.p. Dopamine overflow was measured for at least 2 h postinjection. In the NAC, four postinjection samples were collected once every 30 min. In the STR, eight postinjection samples were collected, once every 20 min. Dopamine baselines in the NAC and STR were 9.22 pg +/- 2.02 and 10.33 pg +/- 2.22 per sample, respectively. In the nucleus accumbens, dopamine release was significantly greater in the group treated with 600 mU insulin (203 +/- 38% of baseline at 30 min). In the STR, increased dopamine release was observed in the groups treated with 200 and 400 mU insulin, whereas a suppression of a dopamine release was observed in the group treated with 600 mU. These data demonstrate that the metabolic state induced by peripheral insulin injection causes dopamine metabolism to change in both the NAC and STR, and at least in part support the hypothesis that insulin may have reinforcing properties in its effect on NAC dopamine release.