Presynaptic Modulation by Cannabinoids

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Science  26 Jan 2001:
Vol. 291, Issue 5504, pp. 555
DOI: 10.1126/science.291.5504.555c

The cannabinoid receptor CB1 is found throughout the body, including the central nervous system, and is thus responsible for all of the central activities of the endocannabinoid system. Two studies apply specific CB1 receptor antagonists and agonists to investigate the mechanisms underlying the modulatory function of endocannabinoid receptor activation.

Gerdeman and Lovinger show that activation of CB1 receptors causes inhibition of glutamate release from afferent presynaptic terminals in the striatum. This inhibition is due to a decrease in release probability at a stage downstream from presynaptic action potentials and Ca2+ channels. By combining immunohistochemistry and electrophysiology, Robbe et al. find that in the nucleus accumbens CB1 receptors are localized on presynaptic excitatory fibers contacting GABAergic neurons. Activation of CB1 receptors, by modulating potassium channel conductances, reduces glutamatergic transmission. This reduced excitation results in decreased firing of the postsynaptic inhibitory cells and may lead in turn to stronger activation of mesolimbic dopamine neurons. — PRS

J. Neurophysiol.85, 468 (2001); J. Neurosci.21, 109 (2001).

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