METHOD FOR SCREENING DRUG AND CHEMICAL EFFECTS IN LABORATORY RATS USING COMPUTERIZED QUANTITATIVE ELECTROENCEPHALOGRAPHY

A minimally-invasive method of quantitive electroencephalography (qEEG ) that requires no anesthetics and parallels techniques of naturalisti c stimulation was developed and validated for regulatory testing of dr ugs and chemicals in rats. Male and female Fischer 344 rats were utili zed ina randomized-block design to measure qEEG target parameters asso ciated with a range of cholinesterase inhibition. For this study physo stigmine was administered ip at doses of 0.05, 0.2 or 1.0 mg/kg, resul ting in average cholinesterase inhibition in plasma (28, 38 and 70%), erythrocytes (19, 24 and 36%), and brain (2, 10 and 31%) which correla ted well with increased total power and amplitude changes. Additional treatment-related effects consisted increased relative alpha and beta, increased relative delta, and a left-shift in the spectral-edge frequ ency. In a second study, male and female Sprague-Dawley rats were util ized in a treatment-by-subjects design to determine qEEG target parame ter changes due to the M(2) autoreceptor agonist oxotremorine. Repeate d incremental doses (0.05, 0.1, 0.2 mg/kg; ip) of oxotremorine resulte d in increased beta contribution, a right-shift in the spectral-edge f requency and decreased alpha contribution. These qEEG results with phy sostigmine and oxotremorine correlate well with receptor-specific and general muscarinic effects, making it a reliable contribution to analy sis of agonist and antagonist effects of cholinergic compounds.