Learning and Memory Enhancement by Neuropeptides

The goal of this research is to discover mechanisms of cognitive enhancement in normal and impaired subjects. Effects of the organometal neurotoxin trimethyltin (TMT) on learning is studied in an autoshaping model, in which rats learn to touch a lever to obtain food. The specific neurotoxic effects of TMT were first observed after accidental exposure of two French chemical workers who experienced memory loss and seizures. Numerous investigations in rodents have confirmed that TMT, administered systemically, produces a relatively specific lesion in hippocampus and related olfactory cortical structures. These lesions are associated with impairments in learning and memory. An initial dose-response study of effects of TMT on autoshaping was completed. Studies showing that rats treated with TMT or a mixed ganglioside preparation (which was administered to determine a possible therapeutic effect in TMT-treated animals) have decreased concentrations of hippocampal glucocorticoid receptors, which may be related to cognitive repairments. A study of the effects of the alpha 2-noradrenergic receptor antagonist yohimbine on autoshapings was completed. This prototypical anxiogneic agent, which increases forebrain norepinephrine release, enhances autoshaping in low doses. Yohimbine also induced increased behavioral arousal, which may account for its effects on autoshaping. Autoshaping is highly dependent upon the deprivation state of the animal: more food deprived rats learn faster.