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Ecstasy is a widely abused psychoactive recreational drug that is known to induce neuroplastic effects. The molecular basis of addiction remains poorly understood, but diverse lines of evidence suggest that neurotrophins (BDNF, NT-3 and NT-4) play a role in the regulation of synaptic plasticity. The present study was designed to evaluate the alteration of NT-4 protein levels and gene expression in the brain stem, cerebellum and cerebral hemisphere of rat brains in the context of ecstasy dependence. Ecstasy addiction was induced by intraperitoneal injection of ecstasy (10 mg/kg) for 5 days. After chronic ecstasy treatment, the NT-4 levels in the abovementioned areas of the brain were determined by ELISA. There was a significant increase in the NT-4 protein concentration in the brain stem, cerebellum and cerebral hemisphere when compared with control group. Additionally, these regions were assayed for the transcription of NT-4 using semi-quantitative RT-PCR normalized to β-actin gene transcription. The results show that chronic administration of ecstasy significantly increased NT-4 gene expression in the abovementioned areas of brain. The current work demonstrates that ecstasy induced-maladaptations may be regulated by NT-4.

Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic double-stranded ribonucleic acid (Poly I: C) during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice. Methods: Male C57BL/6 mice were treated with either saline or Poly I:C (1 mg/kg and 4 mg/kg) on postnatal days (PND) 3-5 (early neonatal phase) or PND 14-16 (late neonatal phase), and then subjected to behavioral tests, including tail suspension test and forced swimming test, during adolescence (PND 35 or 40) and adulthood (PND 85 or 90). Results: The results demonstrated that early neonatal immune activation increases depression-related behaviors in both adolescent and adult mice, but late neonatal immune activation only increases depression in adult mice. In other words, these findings indicated that the nature of the offspring's neuropathology can depend on the severity of the insult, the pup's age at the time of the insult, and offspring age at the time of behavioral testing. Conclusion: These findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric disorders in adults who experienced early life infection.