Genetic dissection of behavioural and autonomic effects of Delta(9)-tetrahydrocannabinol in mice.
PLoS Biol. 2007-10-09; 5(10): e269
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1. PLoS Biol. 2007 Oct;5(10):e269.
Genetic dissection of behavioural and autonomic effects of
Delta(9)-tetrahydrocannabinol in mice.
Monory K(1), Blaudzun H, Massa F, Kaiser N, Lemberger T, Schütz G, Wotjak CT,
Lutz B, Marsicano G.
(1)Department of Physiological Chemistry, Johannes Gutenberg University Mainz,
PLoS Biol. 2007 Oct;5(10):e280.
Marijuana and its main psychotropic ingredient Delta(9)-tetrahydrocannabinol
(THC) exert a plethora of psychoactive effects through the activation of the
neuronal cannabinoid receptor type 1 (CB1), which is expressed by different
neuronal subpopulations in the central nervous system. The exact neuroanatomical
substrates underlying each effect of THC are, however, not known. We tested
locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional
knockout mouse lines, which lack the expression of CB1 in different neuronal
subpopulations, including principal brain neurons, GABAergic neurons (those that
release gamma aminobutyric acid), cortical glutamatergic neurons, and neurons
expressing the dopamine receptor D1, respectively. Surprisingly, mice lacking CB1
in GABAergic neurons responded to THC similarly as wild-type littermates did,
whereas deletion of the receptor in all principal neurons abolished or strongly
reduced the behavioural and autonomic responses to the drug. Moreover, locomotor
and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas
the deletion of CB1 from the majority of striatal neurons and a subpopulation of
cortical glutamatergic neurons blocked the cataleptic effect of the drug. These
data show that several important pharmacological actions of THC do not depend on
functional expression of CB1 on GABAergic interneurons, but on other neuronal
populations, and pave the way to a refined interpretation of the pharmacological
effects of cannabinoids on neuronal functions.
PMID: 17927447 [Indexed for MEDLINE]