The medial prefrontal cortex mediates 3-methoxytyramine-induced behavioural changes in rat

L-3,4-Dihydroxyphenylalanine (L-DOPA) remains a common treatment for Parkinson's disease; however, side effects (i.e., dyskinesia and hallucinations) also remain problematic. We recently reported that the dopamine metabolite 3-methoxytyramine causes stereotypy in rats via dopamine receptors, raising the possibility that 3-methoxytyramine is involved in the adverse side effects of chronic L-DOPA treatment. Thus, the present study examined the sites of 3-methoxytyramine action in the rat brain. After intracerebroventricular administration of 3-methoxytyramine, significantly more neurones expressed c-Fos in mesocortico-limbic dopamine areas including frontal cortex, medial prefrontal cortex, parietal cortex, piriform cortex, the nucleus accumbens shell, and ventral tegmental area. 3-Methoxytyramine injection into the medial prefrontal cortex specifically resulted in behavioural changes characteristic of those elicited by the more general intracerebroventricular injection of 3-methoxytyramine. This suggests that the medial prefrontal cortex mediates the 3-methoxytyramine-induced behavioural changes and that a reduction of its action there may alleviate the adverse effects of chronic L-DOPA treatment.