3. Umbruch 4.4..2005 - Online Pot

118 S.A. Varvel and A.H. Lichtman
Another task that includes some spatial processing requirements is the
delayed-alternation T-maze task. ∆ 9 -THC has been demonstrated to disrupt
performance of rats in a delayed-alternation T-maze task, in which rats were
required to remember which arm had been baited during a preceding sample
trial [41]. These effects occurred at doses that did not interfere with a previously
learned black/white discrimination, a reference-memory task. Similar
effects of ∆ 9 -THC have been demonstrated in mice at a dose that did not affect
choice latency [42]. Intriguingly, others replicated this effect and found that
unlike in the operant tasks described above, tolerance did not develop to
∆ 9 -THC, even after 14 days of twice-daily injections [43].
Conditioned avoidance
Evidence in support of a further delineation of the specificity of cannabinoid
effects on memory comes from several studies in mice that examined the
effects of anandamide in an inhibitory avoidance procedure. In this paradigm,
a chamber or runway is paired with an aversive consequence, most typically
an electric shock. Following the conditioning procedure, the subject is returned
to the apparatus and its memory is assessed by noting its latency to re-enter the
area in which it had previously received the shock. Anandamide administered
immediately after the training trial, but not 2 h after, impaired memory
(decreased latencies) of DBA mice assessed 24 h later [44], suggesting a disruption
of consolidation or encoding processes, since the mice were only susceptible
for a short time following training. This effect appears to be
delay-dependent, as intra-hippocampal administration of anandamide produced
similar deficits in mice tested 24 h after training, while no deficits were
observed when they were tested just 2 h after training [45]. Further work with
this model demonstrated that the disruptive effects of anandamide on memory
consolidation can be amplified by stress, potentiated by a low dose of morphine,
and completely reversed by naloxone [46, 47]. Nonetheless, this effect
appears to be dependent on the strain of mouse, as anandamide inexplicably
appeared to improve memory performance in C57BL/6 mice [48].
In summary, cannabinoid agonists from several different chemical classes, as
well as the endocannabinoid anandamide, tend to selectively disrupt tasks heavily
dependent on working memory, as assessed in a variety of behavioral paradigms,
at doses that do not affect reference memory tasks or produce many
other commonly assessed cannabinoid effects. These effects have been shown
to be mediated via the CB 1 receptor, as they are blocked by CB 1 antagonists and
do not occur in CB 1 –/– mice. Further, the working-memory deficits observed in
the operant DNMS and spatial radial-arm maze tasks have been specifically
linked to effects in the hippocampus, suggesting that endocannabinoids may
play a particularly critical role in this brain area (see below). Many issues related
to the chronic administration of cannabinoids on learning remain unresolved.