CB1 receptor deficiency decreases wheel-running activity: consequences on emotional behaviours and hippocampal neurogenesis.
Experimental Neurology. 2010-07-01; 224(1): 106-113
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1. Exp Neurol. 2010 Jul;224(1):106-13. doi: 10.1016/j.expneurol.2010.01.017. Epub
2010 Feb 4.
CB1 receptor deficiency decreases wheel-running activity: consequences on
emotional behaviours and hippocampal neurogenesis.
Dubreucq S(1), Koehl M, Abrous DN, Marsicano G, Chaouloff F.
(1)AVENIR Team Endocannabinoids and NeuroAdaptation, NeuroCentre INSERM U862,
33077 Bordeaux, France.
Chronic voluntary wheel-running activity has been reported to hypersensitise
central CB1 receptors in mice. On the other hand, pharmacological findings
suggest that the CB1 receptor could be involved in wheel-running behaviour and in
running-induced neurogenesis in the hippocampus. We analysed wheel-running
behaviour for 6 weeks and measured its consequences on hippocampal neurogenesis
in CB1 knockout (CB1(-/-)) animals, compared to wild-type (CB1(+/+)) littermates.
Because wheel running has been shown to affect locomotor reactivity in novel
environments, memory for aversive events and depression-like behaviours, we also
assessed these behaviours in control and running CB1(+/+) and CB1(-/-) mice. When
compared with running CB1(+/+) mice, the distance covered weekly by CB1(-/-) mice
was decreased by 30-40%, an observation accounted for by decreased time spent and
maximal velocity on the wheels. Analyses of running distances with respect to the
light/dark cycle revealed that mutant covered less distance throughout both the
inactive and the active phases of that cycle. Locomotion in an activity cage,
exploration in an open field, and immobility time in the forced swim test proved
insensitive to chronic wheel running in either genotype. Wheel running, per se,
did not influence the expression and extinction of cued fear memory but
counteracted in a time-dependent manner the deficiency of extinction measured in
CB1(-/-) mice. Hippocampal neurogenesis, assessed by doublecortin labelling of
immature neurons in the dentate gyrus, was lowered by 40% in control CB1(-/-)
mice, compared to control CB1(+/+) mice. Although CB1(-/-) mice ran less than
their wild-type littermates, the 6-week running protocol increased neurogenesis
to similar extents (37-39%) in both genotypes. This study suggests that mouse CB1
receptors control wheel running but not its neurogenic consequences in the
Copyright 2010 Elsevier Inc. All rights reserved.
PMID: 20138171 [Indexed for MEDLINE]