Parkinson's disease is a progressive disorder of the central nervous system. Degeneration of the dopaminergic neurons is the main cause of the disease. The basic symptoms of Parkinson's disease are bradykinesia, rigidity and resting tremor. Disturbances of the autonomous nervous system, depression, dementia and sleep disorders are common, too. People with Parkinson's disease suffer from insomni...

The dopamine transporter (DAT) retrieves the neurotransmitter dopamine from the synaptic cleft at dopaminergic synapses. Variations in solute carrier family 6A, member 3 (SLC6A3/DAT1), the human gene encoding DAT, have been implicated in attention deficit hyperactivity and bipolar disorders, and DAT is a prominent site of action for drugs such as amphetamines and cocaine. In this issue of the J...

Cell-gene therapy is a dynamic constituent of novel medical biotechnology. Neurodegenerative disorders in which damage to or demise of specific brain cell types plays central role, are clear examples of disease candidate for cell replacement therapy. Dopaminergic (DAergic) neurons biosynthesize dopamine, a vital neurotransmitter in the central nervous system. Due to the involvement of dopamine ...

The recent identification of the trace amine-associated receptor (TAAR)1 provides an opportunity to dissociate the effects of trace amines on the dopamine transporter from receptor-mediated effects. To separate both effects on a physiological level, a Taar1 knockout mouse line was generated. Taar1 knockout mice display increased sensitivity to amphetamine as revealed by enhanced amphetamine-tri...

Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA signaling in mesolimbic neurotransmission are widely believed to modify reward-related behaviors and are therefore closely associated with drug addiction. Recent evidence now suggests that as with drug addiction, obesity with compulsive eating behaviors involves reward circuitr...

Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotyp...

D(1) dopamine receptors are primary mediators of dopaminergic signaling in the CNS. These receptors internalize rapidly following agonist-induced activation, but the functional significance of this process is unknown. We investigated D(1) receptor endocytosis and signaling in HEK293 cells and cultured striatal neurons using real-time fluorescence imaging and cAMP biosensor technology. Agonist-i...

Phasic firing changes of midbrain dopamine neurons have been widely characterized as reflecting a reward prediction error (RPE). Major personality traits (e.g., extraversion) have been linked to inter-individual variations in dopaminergic neurotransmission. Consistent with these two claims, recent research (Smillie et al., 2011; Cooper et al., 2014) found that extraverts exhibited larger RPEs t...

The present study examined the influence of alpha-2 adrenoceptor ligands on circling behavior in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. The alpha-2 adrenoceptor agonists, clonidine and UK 14304, inhibited both the ipsilateral rotation induced by the indirect dopaminergic agonist, methylphenidate, and the contralateral circling induced by the direct dopamine...

Dopamine abnormalities underlie a wide variety of psychopathologies, including ADHD and schizophrenia. A new imaging technique, pharmacological magnetic resonance imaging (phMRI), is a promising non-invasive technique to visualize the dopaminergic system in the brain. In this review we explore the clinical potential of phMRI in detecting dopamine dysfunction or neurotoxicity, assess its strengt...