Pharmacology Biochemistry & Behavior, Vol. 8, pp. 137-141. Printed in the U.S.A. Evoked Potential Alterations Following Prenatal Methyl Mercury Exposure ROBERT S. DYER, 2 CHRISTINE U. ECCLES AND ZOLTAN ANNAU Department of Environmental Health Sciences, Johns Hopkins UniversiO', 615 N. Wolfe St., Baltimore, MD 21205 (Received 30 July 1977) DYER, R. S., C. U. ECCLES AND Z. ANN AU. Evoked potential alterations,following prenatal methyl mercury exposure. PHARMAC. BIOCHEM. BEHAV. 8(2) 137-141, 1978. - Pregnant hooded rats were administered either 5 mg/kg CH3 Hg or 0 mg/kg CH3 Hg by gastric intubation on day seven of gestation. Female offspring were implanted with recording electrodes 60 days alter birth and had their cortically recorded visual evoked potentials studied at four different flash intensities. Mercury exposed animals had higher P1-NI and N1-P2 amplitudes and shorter P2 and N2 latencies than controls. The data provides evidence that a single ingestion of CHa Hg by pregnant rats is sufficient to produce long term alterations in CNS activity. Prenatal Methyl mercury Visual evoked potentials Hooded rats Females Toxicity METHYL mercury (CH 3 Hg) is known to be a potent neurotoxin which in sufficient quantities produces a variety of symptoms, including peripheral neuropathies [4], visual deficits [6] and cerebellar degeneration [12]. In addition to these effects of frank methyl mercury intoxication, more subtle effects have been observed to result from low level exposure. Indeed, exposure of pregnant mice to doses of CH 3 Hg which produce no obvious impairment in the mothers are clearly capable of producing CNS damage to the offspring [ 9,13 ]. Recently electrophysiological methods have been used to detect CNS damage induced by exposures to organic Hg [11,15]. It was reported that in anesthetized rats, the cortically recorded somatosensory evoked potential wave- form began to change after 18 daily IP injections of 2 mg/kg methoxy-ethyl-mercury chloride [11]. The changes reported were characterized by gradually increasing latencies of late peaks in the evoked potential. When flash evoked potentials were recorded from the cortex of anesthetized 30 day old male offspring of albino rats exposed to 2.5 mg/kg/day CH 3 Hg in their drinking water throughout pregnancy, latencies were decreased [ 15 ]. These results are puzzling, first because they are quite different from those reported for somatosensory evoked potentials, and secondly because it is difficult to under- stand how CH 3 Hg could increase conduction velocity. Both experiments suffer from the shortcoming of having failed to adequately measure evoked potential amplitudes, and both were performed upon chloralose anesthetized animals. In the present experiment an attempt was made to improve the sensitivity of the evoked potential technique by making recordings from unanesthetized animals and including amplitude measurements as part of the protocol. METHOD Long-Evans hooded rats were obtained from Blue Spruce Farms and housed in the laboratory for two weeks before breeding. Experienced males were then placed with naive females weighing between 270 and 320 g. Twelve hr later vaginal smears were taken, and if found to be sperm positive the females were immediately removed and housed individually. On gestational Day 7, four pregnant rats were given a single dose of 5 mg/kg CH3 Hg as CH3 Hg Cl dissolved in corn oil and administered by gastric intubation. This dose was chosen to be representative of those low doses at which behavioral effects had been reported in mice [9]. Six pregnant control rats received corn oil alone. Litters were reduced to eight on Day l post-partum (average pup weight 64.0 g control, 64.8 g methyl mer- cury), weaned at 22 days of age (average pup weight 45.7 control, 53.3 methyl mercury), and housed by sex in groups of 2-4 until Day 65. On Day 65, the males were removed for subsequent testing and the females (average weight 244 g for controls, 258 for methyl mercury) were anesthetized with 0.3 ml/100 g of Equithesin and implant- ed with 0-80 x i/16 in. stainless steel screws for recording the cortical evoked potential. The active screw was placed 5.0 mm posterior to bregma and 3.0 mm lateral to the midline, the reference screw was placed 1.0 mm anterior to Supported in part by NIH grants 054053 and EHS 00454. 2 Present address: Laboratory of Neuroscience, National Center for Toxicological Research, Jefferson, AR 72079. 137 0091-3057/78/0802-0137500.75 Copyright © 1978 ANKHO International Inc.