Androgen modulation of MPP+- induced Dopamine release in the Corpus Striatum and Nucleus Accumbens of male rats, /

Abstract

Parkinson's disease is a progressive, neurodegenerative disorder of unknown cause found in elderly individuals. Its symptoms, such as uncontrolled tremors, difficulty in walking, and depression, are primarily due to low levels of the neurotransmitter, dopamine, which plays a major role in motor function. It has been demonstrated that specific cell death progressively occurs in the substantia nigra, a brain region rich in dopamine-containing neurons. This dopaminergic cell loss results in dopamine depletion in the neuron terminals found in the corpus striatum and nucleus accumbens. Furthermore, there seems to be evidence pointing to certain gender differences associated with Parkinson's disease, which suggests possible involvement of gonadal steroid hormones.

In order to better understand the processes involved, experiments have used the neurotoxin, MPP+, which selectively destroys dopaminergic neurons. However, acute administration of MPP+ stimulates dopamine release and prolongs its presence in the synaptic cleft by interfering with its re-uptake mechanism into the nerve terminals. The present study focused on the potential effects of castration in modulating the dynamics of acute MPP+- induced dopamine release from the corpus striatum and nucleus accumbens in male rats. The technique of in vivo voltammetry was utilized for direct monitoring of evoked dopamine releases in these brain regions. Results confirmed that specific dopamine release characteristics were suppressed following MPP+ infusion in both the corpus striatum and nucleus accumbens when compared to potassium-stimulated responses. Results also demonstrated that MPP+ was more effective in the nucleus accumbens than in the corpus striatum, suggesting a difference in sensitivity to this neurotoxin. Furthermore, castration altered the effects ofMPP+ in the nucleus accumbens suggesting that androgens may act in this brain region to influence the action of this neurotoxin in this area.