Parkinson’s disease (PD) is a neurodegenerative disorder with no cure and treatments with limited efficacy. We have recently observed that the CRF-like peptide urocortin (UCN) reverses key features of nigrostriatal neurodegeneration in the 6-hydroxydopamine (6-OHDA) hemiparkinsonian rat, (Biggs et al., 2006; Abuirmeileh et al. 2007). While these data strongly indicate restoration of nigrostriatal integrity we are unsure if they reflect a restoration of striatal extracellular DA levels. To address this we have measured basal and evoked extracellular striatal DA using microdialysis in freely moving rats. Male Wistar rats (250-280g-1; n = 4-6 per group) were anaesthetised with isofluorane and stereotaxically injected with 6-OHDA or UCN (T0) as previously described (Biggs et al. 2006) In some experiments UCN was given 7 days after 6-OHDA (T+7). 14 days after 6-OHDA, rats were given 0.5 mg kg/kg of apomorphine to evaluate ipsilateral circling, after which they were implanted with dialysis probes (under isofluorane anaesthesia) as previously described (Whitton et al., 1992), and 24h later perfused with artificial cerebrospinal fluid (Whitton et al., 1992) at 1.0µl/min. After 1 h, 4 x 30 min samples were collected prior to infusion of 100mM K+ (substituted for equimolar Na+) for 30 min, and collection two further 30 min samples. DA was estimated as previously described (Biggs et al., 2006). Data were subjected to two way ANOVA and Dunnett’s post hoc test. Compared to rats given 6-OHDA alone, apomorphine induced circling behaviour was greatly attenuated by injection of UCN (25.6 ± 3.77 vs 6.51 ± 1.2 and 8.43 ± 2.2 turns/120 s for 6-OHDA, 6-OHDA + UCN (T0) and 6-OHDA + UCN (T+7) respectively, p<0.05). Sriatal dialysis of shams showed basal extracellular DA at 28 ± 2.7 fmol/10ul (mean ± s.e.mean, n= 10) and this was increased to around 1000 fmol/10ml by K+ infusion. 6-OHDA reduced both basal and stimulated DA levels by between 80-90 %. However, when UCN was given either concomitantly with the toxin (T0) or seven days later (T+7) basal and evoked extracellular DA was comparable to Sham treated controls. These data provide further evidence for a potential neuroprotective role for UCN in models of PD. Two key points arise from these findinds. Firstly, since UCN can restore striatal extracellular DA concentrations this indicates that local DA receptors will be engaged and we presume this underlies the restoration of motor deficits. Secondly, the observation that UCN reverses motor and neurochemical deficits when given at T+7 indicates that it is capaple of effecting restoration once the lesion has become established (Abuirmeileh et al., 2007). These observations suggest that UCN or similarly acting molecules offer therapeutic promise in PD.