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aspects of learning and memory of humans (see [16, 17] for review) and in
animal models of learning and memory (see Tab. 1 for an overview of rat,
mouse, and nonhuman primate studies). Such deficits resulting from administration
of ∆ 9 -THC and other cannabinoids have come under increasing
scrutiny in recent years as new tools have become available, and as it has
become clear that these deficits are the result of interactions with an endocannabinoid
system that may play a crucial role in the physiological basis of
learning and memory.
One strategy for investigating the role that the endocannabinoid system may
play in learning and memory processes is through the use of animal learning
models. While it is certain that exogenous administration of an agonist cannot
closely mimic the actions of an endogenous system tightly integrated within
neural circuits sensitive to specific spatio-temporal contexts, useful information
about the endogenous system can be taken from these studies. For example,
those particular memory tasks that are particularly sensitive to disruption
by exogenous agonists may provide insight into processes that are modulated
by endocannabinoids. Conversely, endocannabinoids are probably not crucial
to aspects of memory that are insensitive to disruption by exogenous agonists.
So which aspects of learning and memory appear most sensitive to agonists?
The most consistent delineation made regarding the effects of CB 1 agonists is
that they tend to disrupt aspects of short-term (i.e. working) memory, while
leaving retrieval of well-learned information (i.e. long-term or reference memory)
largely intact. Working memory is an evolving concept reflecting those
processes necessary to learn and react to new information that changes over
time – a mnemonic whiteboard of sorts. Clearly, the term working memory
encompasses many distinct processes, including attentional mechanisms, as
well as associational, consolidation, encoding and retrieval processes.
Determining the impact of CB 1 agonists on these components is the focus of
ongoing investigation. The section below reviews many of the key studies that
address this issue by using a variety of animal models of cognition, including
instrumental operant tasks, spatial maze paradigms, and conditioned avoidance
tasks.
A major consideration in animal models of cognition is that learning and
memory is not directly measured, but is inferred based on changes in performance.
In particular, alterations in attentional, sensorimotor, and motivational
processes can affect performance, independently of cognition. These
potential confounds are of considerable concern in investigating the role of the
endogenous cannabinoid system, as cannabinoid agonists and antagonists as
well as CB 1 –/– mice are known to affect many non-mnemonic functions that
could impact specific animal models of learning, including locomotor activity,
motivation, feeding behavior, and anxiety. In addition, there are many types of
short-term and long-term memory that are reflected in a diversity of animal
models, including recognition tasks, spatial tasks, food-motivated operant
behavior, and fear-conditioning procedures. Moreover, within each particular
form of memory, multiple processes are involved including acquisition, con-