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2017 ; 170
(ä): 141-150
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Circulating levels of endocannabinoids respond acutely to voluntary exercise, are
altered in mice selectively bred for high voluntary wheel running, and differ
between the sexes
#MMPMID28017680
Thompson Z
; Argueta D
; Garland T Jr
; DiPatrizio N
Physiol Behav
2017[Mar]; 170
(ä): 141-150
PMID28017680
show ga
The endocannabinoid system serves many physiological roles, including in the
regulation of energy balance, food reward, and voluntary locomotion. Signaling at
the cannabinoid type 1 receptor has been specifically implicated in motivation
for rodent voluntary exercise on wheels. We studied four replicate lines of high
runner (HR) mice that have been selectively bred for 81 generations based on
average number of wheel revolutions on days five and six of a six-day period of
wheel access. Four additional replicate lines are bred without regard to wheel
running, and serve as controls (C) for random genetic effects that may cause
divergence among lines. On average, mice from HR lines voluntarily run on wheels
three times more than C mice on a daily basis. We tested the general hypothesis
that circulating levels of endocannabinoids (i.e., 2-arachidonoylglycerol [2-AG]
and anandamide [AEA]) differ between HR and C mice in a sex-specific manner.
Fifty male and 50 female mice were allowed access to wheels for six days, while
another 50 males and 50 females were kept without access to wheels (half HR, half
C for all groups). Blood was collected by cardiac puncture during the time of
peak running on the sixth night of wheel access or no wheel access, and later
analyzed for 2-AG and AEA content by ultra-performance liquid chromatography
coupled to tandem mass spectrometry. We observed a significant three-way
interaction among sex, linetype, and wheel access for 2-AG concentrations, with
females generally having lower levels than males and wheel access lowering 2-AG
levels in some but not all subgroups. The number of wheel revolutions in the
minutes or hours immediately prior to sampling did not quantitatively predict
plasma 2-AG levels within groups. We also observed a trend for a
linetype-by-wheel access interaction for AEA levels, with wheel access lowering
plasma concentrations of AEA in HR mice, while raising them in C mice. In
addition, females tended to have higher AEA concentrations than males. For mice
housed with wheels, the amount of running during the 30min before sampling was a
significant positive predictor of plasma AEA within groups, and HR mice had
significantly lower levels of AEA than C mice. Our results suggest that voluntary
exercise alters circulating levels of endocannabinoids, and further demonstrate
that selective breeding for voluntary exercise is associated with evolutionary
changes in the endocannabinoid system.