3. Umbruch 4.4..2005 - Online Pot

116 S.A. Varvel and A.H. Lichtman
crimination) required rats to press one of two levers in the presence of an
auditory or visual stimulus in a test of reference memory, while the other
component (delayed non-match to position) required rats to press the lever
opposite the one that was appropriate for the first component – a test of working
memory. Consistent with a CB 1 receptor mechanism of action, the selective
deficits produced both by ∆ 9 -THC and anandamide in this task were
reversed by SR-141716 [23]. Others have examined slightly different aspects
of learning with other variations of operant tasks. For example, ∆ 9 -THC and
methanandamide (an anandamide analog resistant to degradation) disrupted
the repeated acquisition of a series of three responses in an
SR-141716-reversible manner, though only at doses which also reduced
response rates [24]. A refinement of this procedure added a performance component
in which rats executed a previously learned series of responses that
remained the same across sessions. ∆ 9 -THC reduced accuracy and rate of
responding in both components, and as with the DNMS studies mentioned
above, tolerance developed to these effects after daily administration [25].
Unfortunately, the sensitivity of the performance requirements of these tasks
to ∆ 9 -THC-induced disruptions (as measured by response rates) precluded a
straightforward interpretation regarding the selectivity of ∆ 9 -THC’s effects.
Interestingly, ∆ 9 -THC-induced deficits in this task were shown to be sensitive
to estrogen, suggesting that sex differences may play an important modulatory
role on cannabinoids effects on learning [26].
A series of experiments in rhesus monkeys tested the effects of ∆ 9 -THC or
marijuana smoke on performance in a battery of instrumental tasks designed
to assess different aspects of learning and memory [27, 28]. Both ∆ 9 -THC and
marijuana smoke produced the most profound deficits in a temporal response
differentiation task and a DMTS task. They also produced moderate disruptions
of conditioned position responding and incremental repeated acquisition
tasks, and were least disruptive of a progressive ratio task. Further studies with
rhesus monkeys as well as squirrel monkeys have also demonstrated that
∆ 9 -THC as well as WIN-55,212-2 disrupted a repeated acquisition performance
that was reversed by SR-141716 [29, 30]. Finally, another study showed
that performance of a similar DNMS task was disrupted at doses of ∆ 9 -THC
that did not interfere with a concurrent discrimination task [31], also consistent
with a specific deficit in working memory processes.
Spatial tasks
Tests of spatial learning and navigation take advantage of strategies that animals
use for foraging and avoidance of predators in their natural environment and
represent an important approach to investigations of learning and memory. One
such spatial memory task that has been used to study the effects of ∆ 9 -THC on
spatial learning is the eight-arm radial maze, which requires rats to learn which
arms contain food rewards, and to remember which arms have already been vis-