ASSOCIATIVE AND LIMBIC REGIONS OF MONKEY STRIATUM EXPRESS HIGH-LEVELSOF DOPAMINE D-3 RECEPTORS - EFFECTS OF MPTP AND DOPAMINE AGONIST REPLACEMENT THERAPIES

The role of the dopamine Dg receptor subtype in the central nervous sy stem is still not well understood. It has a distinct and restricted di stribution, mostly associated with limbic territories of the striatum (olfactory tubercle and the shell of nucleus accumbens) in rat brain, Dopaminergic denervation induced by a 6-hydroxydopamine lesion of the nigrostriatal system in rat down-regulates the expression of the D-3 r eceptor. In the present study, we investigated the functional neuroana tomy of the dopamine Dg receptor subtype in the monkey (Macaca fascicu laris) basal ganglia. We also studied the effect of administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridi ne (MPTP) and chronic D-1-like (SKF 82958) or D-2-like (cabergoline) a gonist treatments on dopamine D3 receptor levels using receptor autora diography. Our results clearly show that the distribution of D3 recept ors in the monkey is more closely related to associative and limbic co mponents of the striatum (caudate-putamen), as compared with its senso rimotor counterpart. Hence, D-3 receptors may be more specifically inv olved in cognitive and motivational aspects of striatal functions, whi ch are elaborated in prefrontal, temporal, parietal, cingulate and lim bic cortices. Moreover, MPTP administration significantly decreased le vels of D-3 receptors and this effect was reversed or compensated by a chronic treatment with a D-1-like, but not a D-2- like, receptor agon ist. The D-3 receptor may represent an important target for adjunct or direct therapy designed to improve cognitive deficits observed in pat ients with Parkinson's disease, schizophrenia and other illnesses with frontal lobe cognitive disturbances.