Participation of the Cholinergic System in Ameliorating Effect of Vasopressin Fragment by Group I Metabotropic Glutamate–Receptor Blockade

The effect of [pGlu4,Cyt6,Arg8]-vasopressin fragment 4-9 (AVP4-9) on group I metabotropic glutamate (mGlu1) receptor antagonist–induced memory deficits was studied using 8-arm radial maze performance with 4 arms baited. In addition, the participation of the cholinergic system in the ameliorating effect of AVP4-9 on mGlu1 receptor antagonist–induced memory deficits was also investigated. Intrahippocampal injection of (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA), an mGlu1-receptor antagonist, significantly increased total error, reference memory error, and working memory error at a dose of 20 nmol/side. AVP4-9 (0.1 and 1.0 μg/kg, s.c.) showed a significant ameliorative effect on AIDA-induced memory deficits. Improvement of AIDA-induced memory deficit in response to AVP4-9 treatment was significantly antagonized by scopolamine (5 nmol/side) but not by mecamylamine (200 nmol/side) at a dose that caused no effect on performance when injected separately. These findings indicate that the ameliorating effect of AVP4-9 on AIDA-induced memory deficit may be closely associated with the muscarinic receptor.