Could Sigma Receptor Ligands be a Treatment for Methamphetamine Addiction?

Kelli      R. Rodvelt; Dennis      K. Miller

doi:10.2174/1874473711003030156

Abstract

Methamphetamines effects are generally considered to be mediated via monoamine transporters; however, it has comparable affinity for sigma receptors. Sigma receptors influence the downstream dopamine systems that are targeted by methamphetamine treatment. Research investigating the effect of sigma receptor agonists on methamphetamine-associated neurochemical and behavioral properties remains controversial; however, the general trend indicates an enhancement of stimulant effects. In contrast, sigma receptor antagonists attenuate methamphetamine-induced neurotoxic and behavioral properties. Together, these studies highlight an important role for sigma receptors in methamphetamines addictive properties and the consequences of methamphetamine intoxication. Additional research is necessary to elucidate the precise mechanisms underlying their involvement and their role as a potential target for antimethamphetamine pharmacotherapies.

Keywords: Methamphetamine, sigma receptors, locomotor activity, sensitization, drug discrimination, psychostimulant, wakefulness, paranoid psychosis, replacement therapies, Antidepressant drugs, monoamine neurotransmitters, mirtazapine, noradrenergic, monoamine oxidase inhibitors, buproprion, ionotropic glutamate receptors, serotonin, catecholamines, substantia nigra, limbic system, several midbrain subregions, benzomorphans, N-dimethyltryptamine, dehyroepianderosterone (DHEA), neurotransmitter systems, chaperoning IP3 receptors, plasmalemmal ion, di-o-tolylguanidine (DTG), postsynaptic effects, Manipulation, locomotor stimulatory, cyclic guanosine monophosphate, pentazocine, nicotine-evoked, tyrosine hydroxylase activity, hyperthermia, presynaptic dopamine, neurochemical