Effect of (192)IgG-saporin injections into the nucleus basalis magnocellularis on acquisition and performance of a go/no-go procedure in the rat

The effects of injections of low (105 ng) and high (210 ng) doses of the ch olinergic-selective neurotoxin (192)IgG-saporin (SAP) into the nucleus basa lis magnocellularis on both the acquisition and performance of a go/no-go o perant task in Long-Evans rats were examined and were correlated with regio nal changes in choline acetyltransferase (ChAT) activity. The go/no-go proc edure rewards a rat for pressing a lever on alternate trials, with intertri al intervals (i.e., delays) of 5, 20, and 40 sec. Over a period of 15 days, normal rats rapidly become proficient in this task, so that the ratio of l atency to the first press on the rewarded go trial to latency to press on t he nonrewarded no-go trial is significantly less than 1. With injections ma de prior to acquisition. there was a significant disruptive effect of both doses of SAP that was not delay dependent. In previously trained rats, SAP disrupted performance during a 2-week training period, with the high dose o f SAP having a more pronounced effect. A uniform 60% reduction of cortical ChAT activity relative to control was found after either high- or lour-SAP injections; however, there was a dose-dependent reduction in hippocampal Ch AT activity with SAP treatment (low dose [20%-29%] and high dose [39%-44%]) . Thus. the dose-dependent disruption in rats trained prior to injection ma y be related to combined cortical and hippocampal cholinergic deficits. The presence of an impairment at even the shortest delay suggests that impaire d working memory may play only a minor role in the go/no-go deficit produce d by disruption of the basal forebrain cholinergic system and that impaired attention may be more important.