METHOD FOR SCREENING DRUG AND CHEMICAL EFFECTS IN LABORATORY RATS USING COMPUTERIZED QUANTITATIVE ELECTROENCEPHALOGRAPHY (REPRINTED FROM VET HUMAN TOXICOL, VOL 37, PGS 616 AND 522-527, DECEMBER 1995)

A minimally-invasive method of quantitative electroencephalography (qE EG) that requires no anesthetics and parallels techniques of naturalis tic stimulation was developed and validated for regulatory testing of drugs and chemicals In rats. Male and female Fischer 344 rats were uti lized In a randomized-block design to measure qEEG target parameters a ssociated with a range of cholinesterase inhibition. For this study, p hysostigmine was administered ip at doses of 0.05, 0.2 or 1.0 mg/kg, r esulting in average cholinesterase inhibition In plasma (28, 38 and 70 %), erythrocytes (19, 24 and 36%), and brain (2, 10 and 31%) which cor related well with increased total power and amplitude changes. Additio nal treatment-related effects consisted of decreased relative alpha an d beta, increased relative delta, and a left-shift in the spectral-edg e frequency. In a second study, male and female Sprague-Dawley rats we re utilized in a treatment-by-subjects design to determine qEEG target parameter changes due to the M(2) autoreceptor agonist oxotremorine. Repeated incremental doses (0.05, 0.1, 0.2 mg/kg; ip) of oxotremorine resulted in increased beta contribution, a right-shift in the spectral -edge frequency and decreased alpha contribution. These qEEG results w ith physostigmine and oxotremorine correlate well with receptor-specif ic and general muscarinic effects, making it a reliable contribution t o analysis of agonist and antagonist effects of cholinergic compounds.