Bidirectional regulation of novelty-induced behavioral inhibition by the endocannabinoid system.
Neuropharmacology. 2009-12-01; 57(7-8): 715-721
DOI: 10.1016/j.neuropharm.2009.07.014
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1. Neuropharmacology. 2009 Dec;57(7-8):715-21. doi:
10.1016/j.neuropharm.2009.07.014. Epub 2009 Jul 14.
Bidirectional regulation of novelty-induced behavioral inhibition by the
endocannabinoid system.
Lafenêtre P(1), Chaouloff F, Marsicano G.
Author information:
(1)INSERM U862 NeuroCentre Magendie Université de Bordeaux, Equipe 8
Endocannabinoids and Neuroadaptation, 146 rue Léo Saignat, 33077 Bordeaux,
France.
The balance between novelty seeking and safety assessment is a key feature of
adaptive behavior, and alterations in this equilibrium can lead to
neuropsychiatric disorders. Excessive novelty seeking is a main form of
pathological impulsivity, which is among the symptoms that define attention
deficit hyperactivity disorder (ADHD). There is growing evidence that the
endocannabinoid system (ECS) plays an important role in the control of this
balance, but little is known about the underlying neuronal mechanisms. In this
study, we aimed at dissecting the neurocircuits under the control of the ECS in
novelty-induced behavioral inhibition. To reach this goal, we combined
pharmacological, genetic and behavioral tools. Mice were repeatedly exposed to
novel palatable food or a novel object and their responses to these stimuli were
analyzed over several days. The results confirmed that systemic blockade of
cannabinoid type-1 (CB(1)) receptors strongly decreases palatable food intake,
but its impact onto the response to novelty is less pronounced. Using conditional
mutant mice lacking the CB(1) receptor either in cortical glutamatergic or in
GABAergic neurons, we found that the ECS exerts opposite functions on the balance
between novelty seeking and behavioral inhibition. Whereas CB(1) receptors
expressed in cortical glutamatergic neurons favors novelty seeking,
CB(1)-dependent control of inhibitory GABAergic neurons promotes behavioral
inhibition. These data show a tightly regulated influence of the ECS on impulsive
behaviors and suggest the involvement of endocannabinoid signaling in the
pathophysiological modulation of ADHD and related disorders.
DOI: 10.1016/j.neuropharm.2009.07.014
PMID: 19607846 [Indexed for MEDLINE]