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Published on: January 22, 2016
Chronic oral methylphenidate treatment in adolescent rats promotes dose-dependent effects on NMDA receptor binding
Khadija Jalloh1, Nicole Roeder2, John Hamilton2
1Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
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.
