We revised our hypothesis that the absence of motor behavior impairments at the presymptomatic stage of Parkinsonism, when degeneration of nigrostriatal dopaminergic neurons has already occurred, is the result of compensatory maintenance of a normal extracellular dopamine (DA) concentration in the striatum. We used microdialysis to measure extracellular levels of DA, its precursor L-dihydroxyphenylalanine (L-DOPA), and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mouse striatum in a model of the presymptomatic stage of Parkinsonism. This stage was induced by a single subcutaneous injection of the neurotoxin precursor 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP) at a dose of 12 mg/kg. At 14 days after MPTP injection, the extracellular DA content substantially decreased as compared to the control; however, it did not result in alterations of motor behavior, probably due to compensatory processes directed, not to the maintenance of extracellular DA at the normal level, but rather to the elevation of neuronal sensitivity to DA. The extracellular L-DOPA content remained at the normal level. We did not find any changes in the DOPAC and HVA contents.Thus, degeneration of DA-ergic striatal axons at the presymtomatic stage of Parkinsonism is associated with a decrease in the DA content in the extracellular space. This indicates that activated compensatory mechanisms are not related to the maintenance of DA concentration in the extracellular space but rather to the increased sensitivity of target neurons to DA.

Several studies on mice have demonstrated a correlation between the concentrations of dopamine and its metabolites in the nucleus accumbens and asymmetry in forelimb preference. Dopamine concentrations were greater in the nucleus accumbens ipsilateral in relation to the preferred paw. Limb preference was demonstrated in rats during performance of a response consisting of withdrawing food from a horizontal tube. Brain tissue dopamine concentrations were estimated by high-performance liquid chromatography with electrochemical detection. The results showed that in "left-handed" rats, the dopamine concentration in the left nucleus accumbens was significantly greater than that in "right-handed" rats. In right-handed rats, the dopamine concentration in the right nucleus accumbens was greater than that in the left. The results obtained here are significantly consistent with data obtained in mice and support the suggestion that the dopamine level in rats is greater in the nucleus accumbens ipsilateral to the preferred limb.

A number of published studies reported a correlation between the paw preference in mice and asymmetry of tissue concentrations of dopamine (DA) and DA metabolites measured in the nucleus accumbens (NAcb) the DA concentration being higher in the nucleus ipsylateral to a preferred paw. This study aimed to investigate whether such asymmetry existed in rats. The paw preference was defined by reaching into a small horizontal tube for a food pellet. Tissue concentration of DA was measured by high-performance liquid chromatography with electrochemical detection. It was shown that the DA concentration in the left NAcb was significantly higher in "left-handed" rats than in "right-handed" animals. Within the group of "right-handers", the DA concentration was significantly higher in the right NAcb than in the left NAcb. The results confirm in part the experimental data obtained in mice and support the hypothesis that the paw preference is paralleled by elevated tissue DA in the ipsylateral NAcb of rodents.