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Chronic oral methylphenidate treatment in adolescent rats promotes dose-dependent effects on NMDA receptor binding

Abstract:

Aim: Examine the effects of chronic oral Methylphenidate (MP) treatment on the N-Methyl-D-aspartic acid (NMDA) glutamate receptor binding in the rat brain using a previously established drinking paradigm that has been shown to deliver MP with similar pharmacokinetic profile as observed clinically. Main methods: Briefly, rats were divided into three treatment groups of water, low dose MP (LD; 4/10 mg/kg), or high dose MP (HD; 30/60 mg/kg). Following a 3-month treatment period, some rats were sacrificed while others went through an additional 1-month abstinence period before they were sacrificed. In vitro autoradiography (ARG) was carried out using [3H] MK801 to examine NMDA receptor binding in the brain. Key findings: The dose-dependent effects of MP following 13 weeks of treatment on [3H] MK-801 binding were seen across the brain in the following regions: prelimbic, insular, secondary motor, primary motor, retrosplenial, rhinal, piriform, auditory, visual, dorsolateral striatum, nucleus accumbens core, hippocampus, amygdala, and thalamic regions. No differences were observed in [3H] MK-801 binding levels in animals that underwent the same treatment followed by a 4 week abstinence. Significance: These results demonstrate that chronic MP treatment altered NMDA receptor expression throughout the brain, which in turn may impact an individual's drug-seeking behavior, fear memory formation and overall activity. However, these effects of chronic MP were eliminated following cessation of treatment.