Changes in dopamine neurotransmission in the nucleus accumbens of the spontaneously hypertensive rat (SHR) may be involved in the pathogenesis of hypertension. This investigation tested the hypothesis that the sulfated octapeptide cholecystokinin (CCK8S) induced release of dopamine is greater in the SHR than in its normotensive control, the Wistar-Kyoto rat (WKY). Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were sampled using microdialysis in the caudal half of the nucleus accumbens of 10-week-old anesthetized SHRs and WKYs. Samples were collected in the following order: 3 baseline, 3 CCK8S (10 mumol/l), and 3 postdrug samples. The samples were then analyzed using high pressure liquid chromatography with electrochemical detection. CCK8S increased dopamine and DOPAC levels in both the SHR and WKY with a larger increase in basal dopamine in the SHR (greater than 200%). Perfusion of the nucleus accumbens with 1 mumol/l of CCK8S or the nonsulfated form of CCK8 (CCK8US, 10 mumol/l) produced no significant increase in the release of dopamine in the SHR. These results indicate that CCK8S-induced release of dopamine in the nucleus accumbens is greater in the SHR. Changes in CCK8S neurotransmission/receptor function may be responsible for the alterations in dopaminergic function of the SHR and the pathogenesis of hypertension.