Melatonin attenuates methamphetamine-induced toxic effects on dopamine and serotonin terminals in mouse brain

Abstract

Methamphetamine (METH) is a drug of abuse that causes deleterious effects to brain monoaminergic systems. These toxic effects are thought to be due to oxidative stress. The pineal hormone, melatonin, has been shown to have neuroprotective effects against toxic quinones and oxidative stress produced by catecholamines. The present study was thus undertaken to assess possible protective effects of melatonin against METH-induced neurotoxic effects on the striatum and the nucleus accumbens by using autoradiographic techniques. Four dosages (5, 20, 40, 80 mg/kg) of melatonin were administered to mice intraperitoneally 30 minutes prior to the injections of METH (4 x 5 mg/kg) given at 2-hour intervals. The lowest doses of melatonin (5 mg/kg) had no significant effects against METH-induced toxicity. However, the higher doses (40 or 80 mg/kg) of melatonin significantly attenuated METH-induced toxic effects on both dopamine and serotonin systems. These data provide further evidence for a possible role of oxidative stress in METH-induced toxicity.

Melatonin as a Neuroprotective Agent in the Rodent Models of Parkinson’s Disease: Is it All Set to Irrefutable Clinical Translation?

“…Melatonin abolishes methamphetamine-induced degeneration of nerve terminals in the neonatal rat brain and partially restores the expressions of TH, synaptophysin, and growth-associated protein-43 [89]. Melatonin protects the dopaminergic and serotonergic neurons against methamphetamine-generated oxidative stress [90]. On the contrary, melatonin is reported to aggravate the methamphetamine-induced deficits in the serotonergic and dopaminergic systems, such as the suppression of the activities of TH and tryptophan hydroxylase and r ed u c t i o n i n t h e c on t en t s of d o p a m i ne an d 5 -hydroxytryptamine [91].…”

Strain-dependent effects of long-term treatment with melatonin on kainic acid-induced status epilepticus, oxidative stress and the expression of heat shock proteins

“…It has been shown to exert neuroprotective effects against neuronal damage in animal models of neurotoxicity, i.e. stroke and traumatic brain injury (Chung and Han, 2003) as well as toxic quinones and oxidative stress produced by catecholamines (Hirata et al, 1998). Single injection of melatonin in rats before and during the KA-or pilocarpine-induced status epilepticus (SE) has neuroprotective effect by reducing the neuronal death, supragranular mossy fiber sprouting, lipid peroxidation (LP), and microglial activation (Banach et al, 2011;de Lima and Soares, 2005;Guisti et al, 1996).…”

Glial cell survival is enhanced during melatonin-induced neuroprotection against cerebral ischemia

“…Free radical scavengers have been shown to protect against cell death (29,30). Melatonin is a highly potent free radical scavenger (31,32) and its administration to rats has been found to be effective against neurotoxicity (33)(34)(35). The present study explored the utility of melatonin in ameliorating the deficits associated with cerebral ischemia, which are in part mediated by aberrant free radicals and/or reactive nitrogen and reactive oxygen intermediates (e.g., production of nitric oxide, hydrogen peroxide, peroxynitrite).…”