Dysregulation of dopamine transmission is thought to contribute to schizophrenic psychosis and drug dependence. Dopamine release is regulated by D2 dopamine autoreceptors, and D2 receptor ligands are used to treat psychosis and addiction. To elucidate the long-term effects of D2 autoreceptor activity on dopamine signaling, dopamine overflow evoked by single or paired-pulse stimulation was compa...

In addition to being a general anaesthetic, ketamine is a recognized drug of abuse. Many, if not all, drugs of abuse have been shown to increase dopamine efflux in the nucleus accumbens (NAc). As ketamine is optically active, we examined if its actions on dopamine efflux in the NAc were stereoselective. Slices of rat NAc were superfused with artificial CSF at 32 degrees C. Dopamine efflux was e...

Parkinson's disease is a chronic neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Rotenone, a pesticide, produces selective degeneration of dopaminergic neurons and motor dysfunction in rats. To determine the mechanisms underlying rotenone-induced neuronal death, we investigated whether intracellular dopamine plays a role in rotenone (0.1-0.4 mic...

The stimulant drug amphetamine is postulated to enhance dopamine release through the plasmalemmal dopamine transporter by an exchange diffusion with synaptosomal dopamine. Because protein kinase C has been shown to have an effect on dopamine transporter activity, we examined the effect of protein kinase C inhibitors on endogenous dopamine release stimulated by amphetamine in perfused rat striat...

Specific binding of [3H]dopamine to membranes from the corpus striatum of rat and calf brain appears to involve the postsynaptic dopamine receptor. Specific [3H]dopamine binding is saturable, wnd with half-maximal binding in calf membranes at 7 nM. Apomorphine is about twice as potent as dopamine in competing for binding sites, whereas (-)norepinephrine is 5% as potent as dopamine and isoproter...

Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well...

In vitro rotating disk electrode (RDE) voltammetry and in vivo microdialysis were used to characterize dopamine clearance in the rat medial prefrontal cortex (mPFC). RDE studies indicate that inhibition by cocaine, specific inhibitors of the dopamine transporter (DAT) and norepinephrine transporter (NET), and low Na(+) produced a 50-70% decrease in the velocity of dopamine clearance. Addition o...

Dopamine is essential to cognitive functions. However, despite abundant studies demonstrating that dopamine neuron activity is related to reinforcement and motivation, little is known about what signals dopamine neurons convey to promote cognitive processing. We therefore examined dopamine neuron activity in monkeys performing a delayed matching-to-sample task that required working memory and v...

We exposed rat pheochromocytoma PC12 cells to hyperthermia or high dosage of dopamine and examined the direct effects of mild hypothermia or dopamine D(2) receptor agonist. At a hyperthermia of 42-43 degrees C for 120 min there was approximately 50% loss of cell viability accompanied by dopamine overproduction. The model of cell death due to hyperthermia in PC12 cells belonged to the necrotic a...

It has been hypothesized that high-dose methamphetamine treatment rapidly redistributes cytoplasmic dopamine within nerve terminals, leading to intraneuronal reactive oxygen species formation and well characterized persistent dopamine deficits. We and others have reported that in addition to this persistent damage, methamphetamine treatment rapidly decreases vesicular dopamine uptake, as assess...