HIPPOCAMPAL MUSCARINIC RECEPTOR FUNCTION IN SPATIAL LEARNING-IMPAIREDAGED RATS

Efficiency of coupling of hippocampal muscarinic receptors to phosphoi nositide (PI) turnover was investigated in behaviorally characterized young and aged Long-Evans rats using hippocampal minces and the method of partial receptor alkylation of Furchgott. Densities of the m1, m2, and m3 receptor proteins were determined using specific antibodies an d immunoprecipitation. Spatial learning ability was quantified using a water maze. There were no differences in the levels of muscarinic rec eptor proteins between young and aged (27 months) rats or in rats with impaired spatial learning. The dissociation constant (K-D) for the ag onist oxotremorine-M and the K-D/EC(50) ratio, an indicator of recepto r-effector coupling efficiency were similar in young and aged rats. Ho wever, the maximal PI turnover response to oxotremorine-M was decrease d in impaired aged rats and this parameter was highly correlated with the spatial learning index (R = -0.825; p < 0.001). A reduction in eff ector stimulation in the absence of changes in receptor protein or cou pling efficiency suggests that dysfunction in the hippocampal muscarin ic receptor systems occurs at the level of phospholipase C or beyond.