RT Journal Article
SR Electronic
T1 Effects of Exogenous and Endogenous Cannabinoids on GABAergic Neurotransmission between the Caudate-Putamen and the Globus Pallidus in the Mouse
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 608
OP 617
DO 10.1124/jpet.105.092718
VO 316
IS 2
A1 Engler, Birgit
A1 Freiman, Ilka
A1 Urbanski, Michal
A1 Szabo, Bela
YR 2006
UL http://jpet.aspetjournals.org/content/316/2/608.abstract
AB Globus pallidus neurons receive GABAergic input from the caudate-putamen via the striatopallidal pathway. Anatomical studies indicate that many CB1 cannabinoid receptors are localized on terminals of striatopallidal axons. Accordingly, the hypothesis of the present work was that activation of CB1 receptors presynaptically inhibits neurotransmission between striatopallidal axons and globus pallidus neurons. In sagittal mouse brain slices, striatopallidal axons were electrically stimulated in the caudate-putamen, and the resulting GABAergic inhibitory postsynaptic currents (IPSCs) were recorded in globus pallidus neurons. The synthetic cannabinoid receptor agonists R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)-methanone mesylate (WIN55212-2) and (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3-hydroxy-propyl)-cyclohexanol (CP55940) decreased the amplitude of IPSCs. The CB1 receptor antagonist rimonabant prevented the inhibition by WIN55212-2, pointing to involvement of CB1 receptors. Depolarization of globus pallidus neurons induced a weak and short-lasting suppression of IPSCs [i.e., depolarization-induced suppression of inhibition (DSI) occurred]. Prevention of DSI by rimonabant indicates that endocannabinoids released from the postsynaptic neurons acted on CB1 receptors to suppress synaptic transmission. WIN55212-2 did not modify currents in globus pallidus neurons elicited by GABA released from its chemically bound (“caged”) form by a flash pulse, suggesting that WIN55212-2 depressed neurotransmission presynaptically. For studying the mechanism of the inhibition of GABA release, terminals of striatopallidal axons were labeled with a calcium-sensitive fluorescent dye. WIN55212-2 depressed the action potential-evoked increase in axon terminal calcium concentration. The results show that activation of CB1 receptors by exogenous and endogenous cannabinoids leads to presynaptic inhibition of neurotransmission between striatopallidal axons and globus pallidus neurons. Depression of the action potential-evoked calcium influx into axon terminals is the probable mechanism of this inhibition. The American Society for Pharmacology and Experimental Therapeutics