Mechanism of Manganese Dysregulation of Dopamine Neuronal Activity.

Manganese exposure produces Parkinson's-like neurologic symptoms, suggesting a selective dysregulation of dopamine transmission. It is unknown, however, how manganese accumulates in dopaminergic brain regions or how it regulates the activity of dopamine neurons. Our studies in male C57BLJ mice suggest that manganese accumulates in dopamine neurons of the VTA and substantia nigra via nifedipine-sensitive Ca channels.

The sigma-1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction.

Methamphetamine (METH) abuse is a major public health issue around the world, yet there are currently no effective pharmacotherapies for the treatment of METH addiction. METH is a potent psychostimulant that increases extracellular dopamine levels by targeting the dopamine transporter (DAT) and alters neuronal activity in the reward centers of the brain. One promising therapeutic target for the treatment of METH addiction is the sigma-1 receptor (σR).

The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission.

Dopamine neurotransmission is highly dysregulated by the psychostimulant methamphetamine, a substrate for the dopamine transporter (DAT). Through interactions with DAT, methamphetamine increases extracellular dopamine levels in the brain, leading to its rewarding and addictive properties. Methamphetamine also interacts with the sigma-1 receptor (σR), an inter-organelle signaling modulator.