Differential regional effects of methamphetamine on dopamine transport.

Multiple high-dose methamphetamine administrations cause long-lasting (>1 week) deficits in striatal dopaminergic neuronal function. This stimulant likewise causes rapid (within 1 h) and persistent (at least 48 h) decreases in activities of striatal: 1) dopamine transporters, as assessed in synaptosomes; and 2) vesicular monoamine transporter -2 (VMAT-2), as assessed in a non-membrane-associated (referred to herein as cytoplasmic) vesicular subcellular fraction. Importantly, not all brain areas are vulnerable to methamphetamine-induced long-lasting deficits.

Age-dependent effects of methamphetamine on VMAT-2.

Abuse of methamphetamine (METH) among adolescents and young adults is concerning since studies have demonstrated that multiple administrations of high-dose METH induce persistent dopaminergic deficits. METH has also been shown to reduce dopamine (DA) uptake by the vesicular monoamine transporter-2 (VMAT-2) and to reduce the amount of VMAT-2 protein in a purified vesicular fraction. VMAT-2 plays a critical role in the sequestration of DA in dopaminergic nerve terminals.

Age-dependent methamphetamine-induced alterations in vesicular monoamine transporter-2 function: implications for neurotoxicity.

Tens of thousands of adolescents and young adults have used illicit methamphetamine. This is of concern since its high-dose administration causes persistent dopaminergic deficits in adult animal models. The effects in adolescents are less studied.

Dopamine D2 receptor activation increases vesicular dopamine uptake and redistributes vesicular monoamine transporter-2 protein.

Recent studies demonstrate that multiple dopamine receptor subtypes contribute to the regulation of vesicular monoamine transporter-2 (VMAT-2) activity. The present studies extend these findings by demonstrating that administration of the nonselective dopamine D2 receptor family agonist, quinpirole, rapidly increased vesicular dopamine uptake in purified rat striatal vesicles. This effect occurred in both postnatal day 40 and 90 rats, and was associated with redistribution of the vesicular monoamine transporter-2 (VMAT-2) within nerve terminals.

Apomorphine increases vesicular monoamine transporter-2 function: implications for neurodegeneration.

Apomorphine is a nonselective dopamine D1/D2 receptor agonist used in Europe to treat symptoms resulting from the dopaminergic degeneration associated with Parkinson's disease. In addition, neuroprotective effects of this agent in rodent models have been reported. Recent studies indicate that treatments that alter vesicular monoamine transporter-2 (VMAT-2) function may be protective in models of dopaminergic degeneration.

Alterations in vesicular dopamine uptake contribute to tolerance to the neurotoxic effects of methamphetamine.

Previous studies demonstrated that tolerance to the long-term neurotoxic effects of methamphetamine on dopamine neurons could be induced by pretreating with multiple injections of escalating doses of methamphetamine. The mechanism(s) underlying this tolerance phenomenon is unknown. Some recent studies suggested that aberrant vesicular monoamine transporter-2 (VMAT-2) and dopamine transporter function contribute to neurotoxic effects of methamphetamine.

Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson's neurodegeneration.

Pramipexole is a dopamine D2/D3 receptor agonist used to treat Parkinson's disease. Both human and animal studies suggest that pramipexole may exhibit neuroprotective properties involving dopamine neurons. However, mechanisms underlying its neuroprotective effects remain uncertain.