3. Umbruch 4.4..2005 - Online Pot

Role of the endocannabinoid system in learning and memory 119
Most notably, tolerance has been shown to develop to the effects of ∆ 9 -THC in
several operant tasks, but not in the delayed-alternation T-maze.
Endocannabinoid modulation of cognitive processes
Although it is well established that stimulation of CB 1 receptors by exogenously
administered cannabinoids reliably produces potent and fairly specific
memory deficits, the role that the endogenous cannabinoid system plays in
learning and memory is less clear. Even prior to the discovery of anandamide,
tonic activation of the endocannabinoid had been proposed to play a role in an
active forgetting process, in which extraneous information is deleted from
memory storage [78]. Using laboratory animal models, we hope to gain a better
understanding of the role that the endocannabinoid system plays in learning
and memory as well as in neurodegenerative disease states. Below, we
describe evidence suggesting that blocking CB 1 receptors prolongs memory
duration in a variety of animal models of cognition. In addition, there is some
suggestion that this receptor may represent a potential therapeutic target to
treat memory deficits associated with Alzheimer’s disease. However, other
research indicates that disruption of the endocannabinoid system can interfere
with an important component of learning, the process of extinction.
Endocannabinoid modulation of memory duration
The disruption of CB 1 receptor signaling through the use of CB 1 –/– mice and
mice treated with CB 1 receptor antagonists are common approaches to investigate
whether the endocannabinoid system is tonically active in whole animals.
The role that the endocannabinoid system plays in learning and memory
is typically inferred by the manner in which either approach alters performance
in a memory test. The endocannabinoid system appears to play an
inhibitory role on memory duration, as CB 1 –/– mice and SR-141716-treated
animals have exhibited improved performance in several memory tasks (see
Tab. 2). Using a social recognition test, Terranova et al. [13] were the first to
provide in vivo evidence that the endocannabinoid system tonically modulates
memory. In this task a mature rodent spends more time investigating unfamiliar
juvenile conspecifics than familiar ones. Subjects are presented with a juvenile
conspecific on two separate 5-min trials separated by a delay of varying
durations. A decrease in investigative time during the second trial compared
with the first trial indicates that the subject ‘remembered’ the conspecific,
while no difference in investigative time between the two presentations indicates
that it no longer remembers the conspecific. SR-141716 given 5 min after
the first trial dose-dependently enhanced memory 120 min later during the second
trial [13]. The fact that SR-141716 was ineffective when administered at
15 or 90 min after trial 1 suggests the involvement of consolidation processes.