To evaluate the effects of styrene exposure on learning, adult male Long-Evans rats learned repeated reversals of a spatial discrimination task. Styrene monomer (50% vol/vol in corn oil) was administered by gavage to groups of eight rats at 500 mg/kg/day, 5 days/week, for 8 weeks in Experiments (Exps) I and II (total dose = 20.0 g/kg) or for 1,3,5, or 8 weeks in Exp III (total dose = 2.5, 7.5, 12.5, or 20.0 g/kg). Control rats received corn oil vehicle for 8 weeks. Reversal training began 8 (Exp I), 10 (Exp II), or 32 (Exp III) weeks after termination of dosing. In Exp I, an instrumental (IN) schedule was used, under which rats received food after each presentation of a “positive” response lever (S+ ) only if they had made at least one response during that presentation of S+. In Exps II and III, an automaintenance (AU) schedule was used, under which rats received food after every presentation of S+, regardless of responding. In all experiments, a second manipulandum (S°) was presented randomly in time with respect to S + and food delivery. A discrimination ratio (DR) was calculated as the proportion of total responses on S+ in each block of 10 trials. A reversal involved switching the reward values of S+ and S°. Serial reversal learning was quantified in terms of trials to criterion. Reversal learning improved similarly in control and treated rats trained under the IN schedule, whereas treated rats trained under the AU schedule failed to improve as much as controls. Reversal learning of some styrene-treated AU rats in Exp III continued to be impaired for > 1 year after treatment. Increased responding on S° featured prominently in the behavioral effect of styrene. An IN schedule requiring suppression of S° responses for food in Exp III revealed a clear deficit in rats exposed to styrene. Not all treated rats were affected by styrene; nevertheless, changes in the affected individuals were as large as those previously observed after trimethyltin-induced lesions of the CNS. The incidence of impairment was not related to the total dose of styrene given, suggesting the action of other, undetermined factors affecting individual sensitivity to styrene.
Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging
