Cannabinoid function in spatial learning: An update

It has long been known that cannabinoids can alter perception and cognitive function. In this review article, we first discuss the current knowledge of both plant-derived and synthetic cannabinoid effects on learning and memory formation in animals with a particular emphasis on spatial mapping. It appears that stimulation of the cannabinoid receptors in the brain is detrimental to spatial learning, and recent advances suggest that working memory is particularly vunerable and in some cases the involvement of the cannabinoid system in memory consolidation. Most of these effects are mediated by CB₁ receptors, and blockade of these receptors can, under certain conditions enhance learning. In the second part, we investigate whether cannabinoid effects can be explained in terms of modulation of other transmitter systems. Since CB₁ is G-protein-coupled and predominantly presynaptically localised, the primary effect may lie in a down/up-regulation of other transmitters, resulting in memory deficits. Such an analysis proved useful as it revealed that modulation of the noradrenergic and cholinergic system is readily able to explain deficits reported in memory consolidation, while cholinergic, dopaminergic, and GABAergic regulation may explain working memory deficit.