Vesicular monoamine transporter 2

The vesicular monoamine transporter 2 (VMAT2) also known as solute carrier family 18 member 2 (SLC18A2) is a is_associated_with::protein that in humans is encoded by the SLC18A2 is_associated_with::gene. VMAT2 is an is_associated_with::integral membrane protein that transports is_associated_with::monoamines&mdash;particularly is_associated_with::neurotransmitters such as is_associated_with::dopamine, is_associated_with::norepinephrine, is_associated_with::serotonin, and is_associated_with::histamine&mdash;from cellular is_associated_with::cytosol into is_associated_with::synaptic vesicles. In is_associated_with::nigrostriatal pathway and is_associated_with::mesolimbic pathway is_associated_with::dopamine-releasing neurons, VMAT2 function is also necessary for the vesicular release of the neurotransmitter is_associated_with::GABA.

Binding sites and ligands
One binding site is that of dihydrotetrabenazine (DTBZ) and is_associated_with::reserpine. is_associated_with::Lobeline binds at this site. is_associated_with::Amphetamine (TBZ site) and is_associated_with::methamphetamine (reserpine site) bind at distinct sites to on VMAT2 to inhibit its function. Although the amphetamines inhibit VMAT2 presynaptically leading to diminished neurotransmitter, the primary mechanism for the enhancement of extracellular monoamines, like dopamine, is reversal of the is_associated_with::dopamine transporter (DAT). Other VMAT2 inhibitors such as is_associated_with::GZ-793A inhibit the reinforcing effects of methamphetamine, but without producing stimulant or reinforcing effects themselves.

Inhibition of VMAT2
VMAT2 is essential in the presynaptic is_associated_with::neuron's ability to facilitate the release of is_associated_with::neurotransmitters into the synaptic cleft. If VMAT2 function is inhibited or compromised, neurotransmitters, such as is_associated_with::dopamine, cannot be released via normal transport (exocytosis, action potential) into the synapse. VMAT2 function inhibition can have many various effects on neurotransmitter function. Specifically of importance is its effect on the neurotransmitter dopamine.

is_associated_with::Cocaine users display a marked reduction in VMAT2 is_associated_with::immunoreactivity. Sufferers of cocaine-induced is_associated_with::mood disorders displayed a significant loss of VMAT2 immunoreactivity; this might reflect damage to dopamine axon terminals in the is_associated_with::striatum. These is_associated_with::neuronal changes could play a role in causing disordered mood and motivational processes in more severely addicted users.