Variability in neuronal expression of dopamine receptors and transporters in the substantia nigra

Abstract

Background: Parkinson’s disease (PD) patients have increased susceptibility to impulse control disorders. Recent studies suggest that alterations in dopamine receptors in the midbrain underlie impulsive behaviours, and that more impulsive individuals, including patients with PD, exhibit an increase in occupancy of their midbrain dopamine receptors. The cellular location of dopamine receptor subtypes and transporters within the human midbrain may therefore have important implications for the development of impulse control disorders in PD. Methods: The localisation of the dopamine receptors (D1-5) and dopamine transporter proteins in the upper brainstem of elderly adult humans (n=8) was assessed using single immunoperoxidase and double immunofluorescence (with tyrosine hydroxylase to identify dopamine neurons). The relative amount of protein expressed in dopamine neurons from different regions was assessed by comparing their relative immunofluorescent intensities. Results: The midbrain dopamine regions associated with impulsivity (medial nigra and ventral tegmental area, VTA) expressed less dopamine transporter on their neurons than other midbrain dopamine regions. Medial nigral dopamine neurons expressed significantly greater amounts of D1 and D2 receptors, and vesicular monoamine transporter, than VTA dopamine neurons. Conclusions: The heterogeneous pattern of dopamine receptors and transporters in the human midbrain suggests that the effects of dopamine and dopamine agonists are likely to be non-uniform. The expression of excitatory D1 receptors on nigral dopamine neurons in midbrain regions associated with impulsivity, and their variable loss as seen in PD, may be of particular interest for impulse control.