Parkinson’s disease (PD) is an incurable neurodegenerative disorder which can only be treated pallitively. We have recently observed that the CRF-like peptide urocortin (UCN) reverses key features of nigrostriatal degeneration in the lipopolysaccaride (LPS) neuro-inflammatory paradigm of PD (Abuirmeileh et al. 2007). While these findings suggest a restoration of dopaminergic transmission, we are unsure if they reflect a restoration of striatal extracellular DA levels. To address this we have measured basal and evoked striatal DA release using microdialysis in conscious rats. Male Wistar rats (250-280g; n = 4-6 per group) were anaesthetised with isofluorane and stereotaxically injected with LPS or UCN (T0) as previously described (Abuirmeileh et al. 2007) In some experiments UCN was given 7 days after LPS (T7). 14 days after LPS, rats were given 0.5 mg kg-1 of apomorphine to evaluate ipsilateral circling, 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+ (exchanged for equimolar Na+) for 30 min, followed by collection of 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 LPS alone, apomorphine induced circling behaviour was reduced by injection of UCN (18.4 ± 4.01 vs 5.11 ± 1.4 and 8.77 ± 3.06 turns/120 s for LPS, LPS + UCN (T0) and LPS + UCN (T7) respectively, p<0.05). Sriatal dialysis of shams showed basal extracellular DA at 25 ± 3.2 fmol/10ul (mean ± s.e.mean, n= 10) which increased to around 1000 fmol/10ul by K+ infusion. LPS reduced both basal and stimulated DA levels by 70-80 %. However, when UCN was given either at T0 , or 7 days after LPS (T7) basal and evoked extracellular DA was comparable to sham treated rats. These data provide further evidence for a potential neuroprotective role for UCN using a neuro-inflammatory model of PD. This may have particular significance, since neuro-inflammation is currently recieving considerable attention in the aetiology of PD (e.g. see Whitton, 2007). Since UCN can restore striatal extracellular DA concentrations, presumably local DA receptors will be engaged leading to the reversal of motor deficits. The observation that UCN is effective when given at T7 indicates that it is capaple of promoting 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.