Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum.
Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status.
Department of Psychology, University of California, Los Angeles 90095, USA.
Andrew B
AB
Thompson
Department of Psychology, University of California, Los Angeles 90095, USA.
Alexandra
A
Stolyarova
Department of Integrative Biology and Physiology, University of California, Los Angeles 90095, USA.
Zhe
Z
Ying
Department of Integrative Biology and Physiology, University of California, Los Angeles 90095, USA.
Yumei
Y
Zhuang
Department of Integrative Biology and Physiology, University of California, Los Angeles 90095, USA; Department of Neurosurgery, University of California, Los Angeles 90095, USA.
Fernando
F
Gómez-Pinilla
Department of Psychology, University of California, Los Angeles 90095, USA. Electronic address: aizquie@psych.ucla.edu.
Alicia
A
Izquierdo
D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020318:Rats, Long-Evans; D020813:Receptor, trkB / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012420:Running / Q000502:physiology*; D057185:Sedentary Behavior; D014836:Volition
D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; C000607792:DRD2 protein, rat; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D008694:Methamphetamine; D020813:Receptor, trkB
D2 receptors; Frontocortical; Inflammation; Psychostimulant; Striatal; TrkB; Withdrawal