Cannabinoid Function in Learning, Memory and Plasticity 4574.3
Avoidance Tasks
Similar to the fear conditioning paradigms described above, shock is used as
areinforcer when animals aretrained toavoid certain compartments. Twodifferent
training procedures are widely used. Passive or inhibitory avoidance refers to the
active inhibition of a response in order to avoid a footshock; by contrast, active
avoidance refers to behavioural escape from a dangerous area in order to avoid
punishment.
Passive or inhibitory avoidance can be performed in two protocols. In step-
through passive avoidance tasks, animals are released into a brightly lit chamber
and a door is opened to allow entry into a dark compartment. Once entering the
dark compartment, the door is closed and a foot shock is delivered. Upon re-
exposure, animals will prefer to stay in the bright chamber. Step-down inhibitory
avoidance, on the other hand, uses an elevated platform, from which animals will
step down onto a grid floor. This triggers shock delivery and escape back onto the
platform. Memory is assessed in a test session as an increase in step-down latency
relative to the latency observed during acquisition training. As with most shock-
motivated tasks, only a few trials are given to induce long-lasting memory traces.
Mice and rats treated with the endocannabinoid anandamide (1.5–6 mg/kg) im-
mediately post-training presented with a significant memory impairment (Castel-
lano et al. 1997, 1999) when tested in a step-through variant. The block of memory
formation is due to an effect of anandamide on memory consolidation, since
injections 2 h post-training had no effect. Interestingly, this effect was specific
to the CD1 and DBA strains, but memory facilitation was observed in C57Bl/6
mice (Castellano et al. 1999). It is likely that modulation of memory strength with
cannabinoids affected the monoaminergic transmitter system, since both D 1 and
D 2 receptor antagonists reversed deficits induced by anandamide. The memory
deficit was also reversed by naltrexone, an opioid receptor antagonist, suggesting
cross-talk between cannabinoid and opioid system.
Memoryfortheshocktested15minor24hlaterwasalsoreducedinratsinjected
intracerebroventricularly with anandamide or arachidonic acid (3.6 nmol in 5 μl)
immediately post-training (Rodriguez de Fonseca et al. 1998). While anandamide
administration enhanced the amount of slow-wave and rapid eye movement sleep
in the period between training and retention testing, arachidonic acid led to a re-
duction in slow wave sleep. It therefore remains uncertain whether drug-induced
changes in sleep pattern have any bearing on the consolidation and expression
of an inhibitory avoidance response. A more detailed time course with systemic
pre-training, post-training and pre-test injection of∆^9 THC in rats revealed mem-
ory deficits independent of injection time (Mishima et al. 2001). Since no deficit
in acquisition learning was reported, it is safe to assume that cannabinoids have
modulated consolidation and retention processes of emotional memories. Any
functional role for the endocannabinoid system, however, still remains elusive.
Site-direct infusion of anandamide (100 μmol/0.5 μl) into hippocampal CA1 also
induced anterograde amnesia in step-down inhibitory avoidance learning (Barros
et al. 2004).