Decreased spontaneous activity in AMPK α2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism.
It is well known that physical activity has several health benefits, yet many people do not exercise. Dopamine levels in the striatum of the brain are thought to be important for the motivation to exercise. Conversely, we hypothesized that muscle quality can affect the motivation to exercise through alterations of the brain dopamine levels specifically in the striatal region. To test this hypothesis, transgenic mice overexpressing an inactivatable dominant negative α2 AMPK construct (AMPK α2 KD) in muscles and littermate wildtype (WT) mice were tested. AMPK α2 KD mice have impaired running capacity and display reduced voluntary wheel running activity. Striatal content of dopamine and its metabolites were measured under basal physiological conditions and after cocaine-induced dopamine efflux from the ventral striatum by in vivo microdialysis. Moreover, cocaine-induced locomotor activity was tested in an open field test. Furthermore, we investigated maximal running capacity and voluntary running over a period of 19days. AMPK α2 KD mice ran 30% less in daily distance compared to WT. Furthermore, AMPK α2 KD mice showed significantly decreased locomotor activity in the open field test compared to WT when treated with saline or cocaine, respectively, but the increase induced by cocaine was similar in AMPK α2 KD and WT mice. The efflux of dopamine in ventral striatum after cocaine treatment increased similarly by 2.5-fold in the two genotypes, and basal levels of dopamine and its metabolites DOPAC and HVA were also similar between genotypes. These findings show that decreased AMPK activity in muscle leads to decreased voluntary activity which is not due to secondary abnormalities in dopamine levels in the ventral striatum or sensitivity to cocaine. Thus, decreased voluntary activity in AMPK muscle deficient mice is most likely unrelated to regulation of brain dopamine content and metabolism.
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.
Lisbeth L V
LL
Møller
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.
Lykke
L
Sylow
Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
Casper R
CR
Gøtzsche
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.
Annette K
AK
Serup
Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
Søren H
SH
Christiansen
Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen & Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
Pia
P
Weikop
Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
Bente
B
Kiens
Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
David P D
DP
Woldbye
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark. Electronic address: erichter@nexs.ku.dk.
Erik A
EA
Richter
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D009154:Mutation; D012420:Running / Q000502:physiology*
D018765:Dopamine Uptake Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid
AMPK; Exercise; Motivation; Physical activity