At present, whether alpha(2)-adrenoceptors in the prelimbic cortex (PrL) are involved in Parkinson's disease-related anxiety is unclear. We examined the effects of PrL alpha(2)-adrenoceptors on anxiety-like behaviors in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. Compared to the sham operation, the lesion induced anxiety-like responses as measured by the open field test and elevated plus-maze test. Intra-PrL injection of the alpha(2) -adrenoceptor agonist clonidine (1.25, 2.5 or 5 mu g/rat) produced anxiolytic effects in sham-operated and lesioned rats. Furthermore, intra-PrL injection of the alpha(2)-adrenoceptor antagonist idazoxan (1, 2 or 4 mu g/rat) induced anxiogenic effects in two groups of rats. The effective doses produced by clonidine and idazoxan in lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of clonidine (5 mu g/rat) or idazoxan (4 mu g/rat) decreased or increased dopamine (DA) and noradrenaline (NA) and serotonin (5-HT) levels in the medial prefrontal cortex (mPFC) and amygdala in sham-operated and lesioned rats, respectively. These results suggest that alpha(2)-adrenoceptors in the PrL are involved in the regulation of anxiety-like behaviors, which is attributable to changes in DA, NA and 5-HT levels in the mPFC and amygdala after activation and blockade of alpha(2)-adrenoceptors. (C) 2019 Elsevier Inc. All rights reserved.