Biology Reference
In-Depth Information
regions, and thereby contributes to various aspects of brain function including learning and
memory. Thus, the EC system is emerging as a major player in synaptic plasticity. In this
review, the authors describe molecular mechanisms of the endocannabinoid-mediated
synaptic modulation and its possible physiological significance.
Keywords:
endocannabinoids, CNS, synaptic plasticity, CB1 receptors, retrograde signaling,
short-term plasticity, long-term plasticity
2.
I
NTRODUCTION
The earliest anthropological evidence of Cannabis use comes from the oldest known
Neolithic culture in China where it was used in the production of hemp for ropes and textiles,
and also for its psychotropic effects [106] and have been used across various cultures for
centuries [16].
The major psychoactive constituent of Cannabis sativa (such as marijuana, hashish and
bhang) is Δ
9
-tetrahydrocannabinol (Δ
9
-THC, dronabinol), which is mainly responsible for the
pharmacological effects of the Cannabis plant [58, 97]. Currently Δ
9
-THC and its analogs are
used for the treatment of nausea and vomiting induced by radiotherapy or chemotherapy, and
wasting syndrome in AIDS patients. Cannabinoids are also useful for the treatment of pain,
aspasticity, glaucoma and other disorders [210]. However, the clinical usefulness of Δ
9
-THC
and its anlogs is greatly hampered by their profound effects on mental state. These include
euphoric or rewarding properties [131], impairement of attention, working memory [85] and
excutive function [69]. These behavioural effcts are consistent with the findings that Δ
9
-THC
and its analogs (cannabinoids) have widespread actions upon neuronal function in the central
nervous system (CNS).
In recent years, cannabinoid research received a tremendos attention from various
researchers due to the breakthrough and discovery of the receptors that bind Δ
9
-THC
(Cannabinoid receptors) and thier endogenous ligands, endocannabinoids (ECs) in animal
tissues. This emerging body of research has revealed multiple ways in which the
endocannabinoid system functions to regulate synaptic neurotransmission in various brain
areas[118, 156, 212]. Growing research has provided vital functions for EC signaling in
molecular pathways that underlie both short and long lasting alterations in synaptic strength
[2]. Infact, the critical involvement of ECs in some mechanisms of synaptic plasticity may
change the current thinking of cellular models of learning and memory. These models may be
pivotal in understanding and providing potential treatment for the rewarding and amnestic
actions of drugs of abuse including cannabinoids and alcohol.
2.1 Cannabinoid receptors
Cannabinoids have two specific G-protein-coupled heptahelical receptor subtypes, which
have been cloned. These are named CB1 and CB2. Evidence for a third type of G-protein-
coupled cannabinoid receptor (“CB3” or “Anandamide receptor”) in brain and in endothelial
tissues is mounting [28, 60, 104, 207]. However, the cloning, expression and characterization
