The endocannabinoid system: a physiological perspective on its role in psychomotor control

Abstract

The discovery of cannabinoid receptors has led to the identification of two natural activators for these receptors, anandamide and 2-arachidonoylglycerol, and to the elucidation of their biochemical pathways of formation and inactivation. Although the physiological significance of the endogenous cannabinoid system is still poorly understood, important information is becoming available on the possible functional roles of this system in the basal ganglia, a forebrain region that is involved in the control of sensorimotor and motivational aspects of behavior. These discoveries -which are going to enrich the way in which we look at basal ganglia functions -are summarized in this mini-review. The role of the endocannabinoids as modulators of psychomotor behaviors and the potential therapeutic perspectives deriving from the pharmacological manipulation of the endogenous cannabinoid system are also discussed.

Circuitry for Associative Plasticity in the Amygdala Involves Endocannabinoid Signaling

“…Provided that endocannabinoids reduce transmitter release from GABAergic terminals exerting an inhibitory tonus on principal neurons (Giuffrida and Piomelli, 2000), mechanisms critical for learning and memory such as LTP (Watanabe et al, 1995;Huang and Kandel, 1998;Rammes et al, 2000;Chevaleyre and Castillo, 2003) will be favored. LTP of excitatory glutamatergic transmission in the BLA, induced by HFS in the LA, was enhanced by a preceding LFSi.…”

“…Furthermore, endocannabinoids induce a depolarization-induced suppression of inhibition (DSI) in the cerebellum (Kreitzer et al, 2002) and in hippocampal neurons (Ohno-Shosaku et al, 2001;Wilson and Nicoll, 2001). A reduction of transmitter release from GABAergic terminals will eventually reduce an inhibitory tonus exerted on principal neurons (Giuffrida and Piomelli, 2000;Freund et al, 2003). This disinhibition might support mechanisms that are critical for learning and memory, such as longterm potentiation (LTP).…”

Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation

“…Some examples are control of sensorimotor and motivational aspects of behavior (53); regulation of fertilized egg implantation (54); hypotensive and bradycardic effects (55); cognition and drug dependence (56); interplay between the endocannabinoid system and the hormone-cytokine array that is involved in the control of human pregnancy (57); sleep-wakefulness cycle, memory formation, locomotor activity, and pain perception (58); modulation of the immune response (59); and control of pain in parallel with endogenous opioids (60). Anandamide and 2-AG mediate many of their actions via either the CB1 or CB2 cannabinoid receptor subtypes.…”

The Potent Emetogenic Effects of the Endocannabinoid, 2-AG (2-Arachidonoylglycerol) Are Blocked by Δ9-Tetrahydrocannabinol and Other Cannnabinoids

“…In addition, these receptors mediate a transient elevation of intracellular free calcium concentration (Sugiura and Waku, 2000). Identification of specific cannabinoid binding sites has led to the discovery of putative endogenous cannabinoids (endocannabinoids) (Giuffrida and Piomelli, 2000;Sugiura and Waku, 2000). At least two endocannabinoids have been recognized that produce cannabinoid-like effects: 1) arachidonoylethanolamide (anandamide) was the first identified putative endocannabinoid which was originally isolated from porcine brain (Devane et al, 1992), and 2) 2-arachidonoylglycerol (2-AG) was derived from either canine gut (Mechoulam et al, 1995) or rat brain (Sugiura et al, 1995).…”

“…Since both of these agents are rapidly metabolized, the commercially available, more stable analog of anandamide, methanandamide, was also tested. Since more stable analogs of 2-AG are not available to us, and in response to one of the reviewer's request, the possible emetic activity of the common metabolite of the cited endocannabinoids, arachidonic acid (Giuffrida and Piomelli, 2000), was also investigated. The present study was also designed to determine whether cannabinoids of diverse structure and activity (⌬ 9 -THC; WIN 55,212-2; CP 55,940; and cannabidiol) can block emesis produced by endocannabinoids, whether the CB 1 antagonist/inverse agonist SR 141716A modulates emesis produced by endocannabinoids, and whether the emetic property of endocannabinoids is related to established indices of cannabimimetic activity such as reduction in motor activity parameters.…”