Activation and blockade of α2-adrenoceptors in the prelimbic cortex regulate anxiety-like behaviors in hemiparkinsonian rats

Abstract

At present, whether α₂-adrenoceptors in the prelimbic cortex (PrL) are involved in Parkinson's disease-related anxiety is unclear. We examined the effects of PrL α₂-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 α₂-adrenoceptor agonist clonidine (1.25, 2.5 or 5 μg/rat) produced anxiolytic effects in sham-operated and lesioned rats. Furthermore, intra-PrL injection of the α₂-adrenoceptor antagonist idazoxan (1, 2 or 4 μg/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 μg/rat) or idazoxan (4 μg/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 α₂-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 α₂-adrenoceptors.

Keywords: Anxiety; Parkinson's disease; Prelimbic cortex; Rat; α(2)-adrenoceptors.