Somatostatin alleviates impairment of working memory induced by hippocampal muscarinic M1 receptor blockade in rats.

The effects of somatostatin on the impairment of working memory induced in rats by blockade of hippocampal muscarinic M1 or NMDA receptors were examined, using a three-panel runway task. Both the muscarinic M1 receptor antagonist pirenzepine (1.0 microgram/side) and the competitive NMDA receptor antagonist CPP ((+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonoic acid) (32 ng/side) significantly increased the number of working memory errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points), when injected bilaterally into the dorsal hippocampus. This effect of intrahippocampal pirenzepine on working memory was alleviated by concurrent injection of 0.32 microgram/side somatostatin. However, concurrent somatostatin (0.1 or 0.32 microgram/side) had no significant effect on the intrahippocampal CPP-induced increase in working memory errors. These results suggest that somatostatin ameliorates the impairment of working memory resulting from hippocampal muscarinic M1 receptor blockade, possibly through activation of cholinergic functions.