Intrastriatal infusions of methoctramine improve memory in cognitively impaired aged rats.

Alterations of striatal cholinergic markers may correlate with cognitive impairments in aged rats. M2 muscarinic receptors were found to be presynaptic inhibitory autoreceptors on striatal cholinergic interneurons. The effect of bilateral intrastriatal infusions of the M2 muscarinic receptor antagonist methoctramine was assessed, in cognitively impaired aged (24-26 months) Long-Evans female rats, on memory performances in a water maze. Compared with vehicle infusions, methoctramine injected bilaterally (1 microg/side) in the dorsolateral striatum, significantly improved procedural memory performance while having no effect on spatial working memory. Our results suggest that, in cognitively impaired aged rats, the blockade of M2 muscarinic receptors in the dorsolateral striatum improves procedural memory probably by enhancing the release of acetylcholine.