3. Umbruch 4.4..2005 - Online Pot

Role of the endocannabinoid system in learning and memory 121
only effective when given immediately before phase 1, and failed to enhance
memory when administered either immediately after phase 1 or 30 min before
phase 2. In another study, the memory-enhancing effects of SR-141716 in a
delay radial-arm maze task were found to be dose-related and occurred when
administered immediately after the first session, suggesting that the drug
enhanced consolidation processes [52]. However, studies using operant paradigms
have shown no benefits of SR-141716 treatment on performance [20,
23, 24, 53]. In fact, CB 1 –/– mice have been reported to display impaired acquisition
in acquiring lever-pressing response using a simple fixed-ratio schedule
[54]. However, other phenotypes of these mice, including, hypomotility [55],
decreased feeding [8], and altered emotionality [56], may have indirectly disrupted
acquisition through motivational or sensorimotor alterations. One
salient difference between studies in which SR-141716 enhances memory and
those that fail to find any memory improvement is the temporal components of
the task. Memory paradigms that reveal enhancement require memory
processes that are in the order of minutes or hours, while the studies in which
SR-141716 was ineffective require the retention of information that is in the
order of seconds.
Endocannabinoid involvement in neurodegenerative diseases
Alterations of the endocannabinoid system have been reported in at least two
neurodegenerative disease states, suggesting the involvement of this system.
Specifically, reductions of CB 1 receptors were reported in brains of patients
diagnosed with either Alzheimer’s disease [57] or Huntington’s chorea [58]. A
more recent report found that brains from Alzheimer’s disease patients contained
upregulated levels of CB 2 receptors, as well as increased expression of
fatty acid amide hydrolase (FAAH), in microglia associated with β-amyloid
plaques [59]. Preclinical studies investigating the role of the endocannabinoid
system on memory generally utilize young, healthy animals, which arguably
may not be optimal to investigate potential nootropic agents. Conversely, there
is a great multitude of animal models of cognitive dementia and/or memory
impairment that includes surgical procedures, traumatic brain injury, intracerebral
administration of agents, transgenic mice, and drugs. Few studies have
examined the functional role of the endocannabinoid system or cannabinoid-based
therapies in these pathological states or animal models of dementia.
Nonetheless, the fact that SR-141716 attenuated the deficits displayed by
aged mice and rats in the social recognition task suggests that this agent may
have some utility in treating memory deficits that are associated with aging
[13]. Similarly, SR-141716 has been shown to prevent memory deficits in a
passive avoidance task using a rat Alzheimer’s model [60]. In this model, an
intracerebroventricular injection of β-amyloid fragments disrupted memory
when the rats were given the retention test 1 week, but not 1 day, following
acquisition training. SR-141716 given 30 min prior to a 1-week retention test