Release parameters during progressive degeneration of dopamine neurons in a mouse model reveal earlier impairment of spontaneous than forced behaviors

We asked how the ability to release dopamine (DA) relates to the ability to carry out spontaneous, versus forced motor activities, taking advantage of a neurotoxin ‐free transgenic mouse model with degeneration specifically of the DA system. Usingex  vivo fast ‐scan cyclic voltammetry of brain slices, we find that impairment of open field locomotion and rearing began already at 10 weeks, in parallel with a modest decline of evoked DA release while rotarod performance was not impaired until mice were 16 weeks old, when evoked DA release in striatum had decreased to 40% of wild‐type levels. We conclude that forced behaviors, such as motivation not to fall, can be partially maintained even when DA release is severely compromised, whereas spontaneous behaviors are much more sensitive to impaired DA release, and that presumed secondary non‐dopami nergic system alterations do not markedly counteract effects of severe impairment of DA release. AbstractTo determine the role of reduced dopaminergic transmission for declines of forced versus spontaneous behavior, we used a model of Parkinson's disease with progressive degeneration of dopamine (DA) neurons, the MitoPark mouse. Mice were subjected to rotarod tests of motor coordination, and open field and cylinder tests for spontaneous locomotor activity and postural axial support. To measure DA release in dorsal striatum and the shell of Nucleus Accumbens (NAc), we usedex  vivo fast ‐scan cyclic voltammetry in 6‐ to 24...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research