Regional heterogeneity of dopaminergic deficits in vervet monkey striatum and substantia nigra after methamphetamine exposure

Methamphetamine (METH)-induced neurotoxicity within the striatum and substa ntia nigra of the vervet monkey was characterized by heterogeneous decrease s in immunoreactivity (IR) for dopamine system phenotypic markers. Decrease s in IR for tyrosine hydroxylase (TH), dopamine transporter (DAT), and the vesicular monoamine transporter (VMAT2) were observed 1 week after METH HCl (2x2 mg/kg; 24 h apart). Regional changes throughout the rostrocaudal exte nt of the striatum were characterized by a gradient of neurotoxic effect (l ateral greater than medial) and the preservation of patches of IR. The decr eases in IR in the caudate and putamen were greater than those in the nucle us accumbens. The reduced IR in the METH-exposed striatum allowed for the v isualization of dopamine phenotype cell bodies. Within the ventral midbrain , the METH-exposed substantia nigra pars compacta (SNc) also showed a heter ogeneous loss of IR (lateral greater than medial). In contrast, the ventral tegmental area (VTA) showed only minor decreases in IR. The magnitude of t he decreases in the SNc and VTA subregions corresponded to those observed i n their respective striatal projection areas, suggesting that nigrostriatal neuron subpopulations were differentially reactive to METH. The profile of these drug-induced nigrostriatal dopamine system deficits resembles aspect s of Parkinson's disease pathology and, as such, may provide a useful model with which to evaluate neuroprotective and neurorestorative strategies.