Abstract

In this study, the effects intraseptal injections of the selective cholinergic immunotoxin, 192-IgG-saporin, were investigated in mature (6-month-old) and aged (24–26-month-old) male Long-Evans rats. Ten days following intraseptal injection of either 192-IgG-saporin or saline, testing began in a battery of behavioral tests modulated by the septohippocampal system including two versions of the Morris water maze (i.e. submerged platform task, and 2-platform spatial discrimination), inhibitory avoidance, and pre-pulse inhibition of acoustic startle. In both mature and aged rats, intraseptal injection of 192-IgG-saporin selectively reduced ChAT activity in the hippocampus and posterior cingulate cortex, without affecting ChAT activity of amygdala or parietal cortex. In general, in all of the behavioral tests analyzed, intraseptal 192-IgG-saporin treatment had no effect in mature animals. Age-related deficits were observed in the spatial memory tasks, however this impairment was largely a function of the poor performance of aged rats treated with the toxin. In addition, an increase in the response to an acoustic startle was found in aged rats treated with 192-IgG-saporin. Thus, although intraseptal injection of 192-IgG-saporin produced similar reductions of ChAT activity, performance of mature and aged rats in tasks believed to be modulated by the septohippocampal pathway tended to be differentially affected in mature and aged rats.

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