Vitamin E prevents the place learning deficit and the cholinergic hypofunction induced by AF64A

The present study examined whether pretreatment with vitamin E would attenuate the place learning impairment and the neurochemical deficits induced by intracerebroventricular (icv) injection of the cholinotoxin ethylcholine mustard aziridinium ion (AF64A). Male Sprague-Dawley rats were pretreated by intramuscular injection of either vitamin E or saline 24 h and 15 min prior to surgery. They were then infused bilaterally into the cerebroventricles with AF64A (3 nmol/side) or artificial cerebrospinal fluid (CSF). Following 14 days of postoperative recovery, the rats were trained to acquire a place learning task in a water maze for two blocks of four trials a day for 5 days. Following the 40th trial a probe trial was used to assess memory for the platform location. After completion of behavioral testing, hippocampal high-affinity choline uptake (HAChU) was assessed. The groups which had received either saline or vitamin E pretreatment followed by icv injection of CSF did not differ significantly on any parameter measured and were therefore pooled as control group. Animals which had been pretreated with vitamin E and had received icv injection of AF64A exhibited neither significant impairment in water maze performance nor significant decrease in HAChU. In contrast, animals which had been pretreated by saline followed by icv injection of AF64A were significantly impaired in acquisition of the place learning task as well as during the probe trial and had reduced HAChU in the hippocampus. These findings indicate that vitamin E may have a neuroprotective effect in the septohippocampal cholinergic system.