Dose-dependent effects of binge-like methamphetamine dosing on dopamine and neurotrophin levels in rat brain

Abstract

This study investigated the acute effect of a dose range of low-to-moderate binge-like methamphetamine treatments on the regional expression of neurotrophin proteins in the brain and serum 2 h after the last dose, in addition to assessing the behavioural effects and dopamine neurotransmitter changes produced. Male Sprague-Dawley rats received 4 subcutaneous doses of methamphetamine (0.5, 1, 2, and 4 mg/kg, or saline as a control) 2 h apart. Methamphetamine had a dose-dependent stimulatory effect on locomotor activity over the 8 h of observation. A significant increase in dopamine concentration was observed in the frontal cortex with the highest dose of methamphetamine (2 h after the last dose). This effect was dose- and region-specific, as no significant increase was observed with lower doses, nor was a significant change observed in any other brain region tested. A similar dose- and region-specific increase in brain-derived neurotrophic factor (BDNF) was observed in the frontal cortex with the highest-dose regimen. No significant change occurred with lower doses of methamphetamine, or in any other brain region tested. A reduction in BDNF levels in the serum was also observed with the highest concentration, but not with lower doses. Collectively, this data highlights the importance of the frontal cortex in methamphetamine-induced effects, and also the similar dose-response effect of methamphetamine on dopamine and BDNF expression.