Effect of melatonin on d-amphetamine-induced neuroglial alterations in postnatal rat hippocampus and prefrontal cortex

Amphetamine is a psychostimulant drug that produces long-lasting neurotoxic effects on the central nervous system. Recent studies suggested that glia might contribute to amphetamine-induced neuropathy. Excessive activation of astrocytes can be deleterious to the neuron. Amphetamine-induced lesions during development have the potential to produce numerous permanent abnormalities in neural circuitry and function, including memory deficit. In the present study, postnatal rats were injected with either saline or d-amphetamine for 7 consecutive days, starting on postnatal day 4 (P4). Our results found that d-amphetamine caused a marked increase in glia fibrillary acidic protein (GFAP), an astroglia marker, expression that implicated astrogliosis in both hippocampus and prefrontal cortex. The effect of d-amphetamine on hippocampal and prefrontal cortex neurons was also investigated, and we detected a downregulation of βIII-tubulin, a marker of premature neuron expression. Furthermore, we found that pretreatment with melatonin, a major hormone secreted from the pineal gland, prevented glial cell activation and βIII-tubulin reduction, caused by d-amphetamine in both hippocampus and prefrontal cortex. The present study suggests that melatonin can attenuate the detrimental effect of d-amphetamine on glial and neuronal cells.