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Effects of phencyclidine on spontaneous motor activity
NEUROBEHAVIORAL TERATOLOGY SOCIETY ABSTRACTS at the N-methyl-D-aspartate (NMDA) receptor. The NMDA receptor has been shown to play an important role in developmental plasticity. We have earlier shown that postnatal PCP treatment in rats produced long-term changes in seizure susceptibility. Here we report the effects of chronic postnatal PCP treatment on the NMDA receptor distribution pattern. Pups were treated with PCP (5 mg/kg/day) for 11 days from postnatal days 5 to 15, intraperitoneally. Control pups received saline (1 ml/100 g). All rat pups were weaned on postnatal day 21. On postnatal days 21, 40, 60, and 180, separate groups of saline- and PCP-treated rats were sacrificed, their brains removed and immediately frozen in crushed dry ice. Brain sections were incubated with [3H]MK-801 in the absence and presence of excess nonradiolabeled MK-801, washed, dried and juxtaposed against tritium-sensitive film. Quantitative densitometric analyses of the autoradiographic films indicate that postnatal PCP administration produces age-specific alterations in the [3H]MK-801 distribution patterns.
Supl~rtocl by: National Institute on Drug Abuse
NBTS 31 SCALZO, F.M., L.J. BURGE* and F.D. RACEY*, Department of Pediatrics, University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas. Effects of Phencyclidin¢ on Spontaneous Motor Activity. Developmental exposure to phencyclidine (PCP) is thought to have adverse effects on motor control in humans. High doses (> 30 mg/kg) of PCP, administered i.p. to postnatal day (PND) 30 and older rats, produce lesions in discreet brain areas. The mechanism by which these lesions occur and the longlasting behavioral effects of these lesions are poorly understood. We therefore examined the effects of PCP on locomotor activity in adult and periadolescent rats. In addition, pharmacological challenges were used to determine the effects of PCP on specific neurochemical systems known to mediate locomotor activity. Rats were treated on PND 19 with 5 mg/kg PCP and on PND 26 with 30 mg/kg PCP. Another group of rats were treated with 5 mg/kg PCP on PND 60 and 30 mg/kg PCP on PND 67. The number of quadrant entries and total number of left and right turns were measured using an automated activity monitor. In both groups, subsequent to PCP treatment, locomotor activity was also assessed following a saline, 5 mg/kg PCP, 1 mg/kg d-amphetamine, 0.25 mg/kg MK-801 or 3 mg/kg DTG challenge. Treatment with 5 and 30 mg/kg PCP increased the number of entries and both left and right turns at both ages. Treatment with 30 mg/kg PCP did not alter the response to a saline challenge in the PND 60 group. However, in the same group, the total
number of entries and turns were increased in PCP treated rats following a 5 mg/kg PCP challenge. MK801 produced decreased activity in PCP treated rats in the PND 60 group. The results suggest that exposure to a high dose of PCP produces long-lasting alterations in the locomotor response to a PCP and MK-801 challenge. These alterations might be indicative of residual PCP-induced motor deficits. Supported by DA06319.
NBTS 32 WARD*, J.H., K.S. GRANT-WEBSTER, and T.M. BURBACHER, Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle Wa. The effects of in-utero methanol exposure on the development of visual acuitv in infant monkevs. Use of fuel additives without documentation of safety as in the case of lead have resulted in enormous public health consequences. The proposal to add methanol to gasoline or to design automobiles that use methanol as a primary fuel will necessarily widen consumer exposure to this material. The health effects that may be associated with increased environmental exposure to methanol are not well documented at this time. This study provides the f'n'st data on the functional consequences on visual acuity of in-utero exposure to methanol in nonhuman primate infants. Macaca fascicularis females were exposed to either 0 ppm, 200 ppm, 600 ppm or 1800 ppm methanol in air for 2 hours/day, 7 days/week prior to and during pregnancy. Infants were tested at 5 different ages from 1 to 16 weeks of age using black and white stripes of varying widths. The method of choice for assessing infant vision was the two alternative forced-choice preferential looking paradigm. To obtain visual acuity functions, a plot of observer performance versus stripe width is fitted with a curve and the threshold of visual acuity is determined. The performance data from the methanol exposed infants will be compared with the performance of the control subjects to determine whether in-utero methanol exposure is associated with changes in visual acuity. Supported by Grant #90-9 Health Effects Institute.
NBTS 33 GRANT-WEBSTER, K.S., N. A. LIBERATO, and T.M. BURBACHER, Dept. of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle, WA. The Neurobehaviorai Conseouences of InUtero Exuosure to Inhaled Methanol in Macac8 Fascicularis Infants.
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Supl~rtocl by: National Institute on Drug Abuse
NBTS 31 SCALZO, F.M., L.J. BURGE* and F.D. RACEY*, Department of Pediatrics, University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas. Effects of Phencyclidin¢ on Spontaneous Motor Activity. Developmental exposure to phencyclidine (PCP) is thought to have adverse effects on motor control in humans. High doses (> 30 mg/kg) of PCP, administered i.p. to postnatal day (PND) 30 and older rats, produce lesions in discreet brain areas. The mechanism by which these lesions occur and the longlasting behavioral effects of these lesions are poorly understood. We therefore examined the effects of PCP on locomotor activity in adult and periadolescent rats. In addition, pharmacological challenges were used to determine the effects of PCP on specific neurochemical systems known to mediate locomotor activity. Rats were treated on PND 19 with 5 mg/kg PCP and on PND 26 with 30 mg/kg PCP. Another group of rats were treated with 5 mg/kg PCP on PND 60 and 30 mg/kg PCP on PND 67. The number of quadrant entries and total number of left and right turns were measured using an automated activity monitor. In both groups, subsequent to PCP treatment, locomotor activity was also assessed following a saline, 5 mg/kg PCP, 1 mg/kg d-amphetamine, 0.25 mg/kg MK-801 or 3 mg/kg DTG challenge. Treatment with 5 and 30 mg/kg PCP increased the number of entries and both left and right turns at both ages. Treatment with 30 mg/kg PCP did not alter the response to a saline challenge in the PND 60 group. However, in the same group, the total
number of entries and turns were increased in PCP treated rats following a 5 mg/kg PCP challenge. MK801 produced decreased activity in PCP treated rats in the PND 60 group. The results suggest that exposure to a high dose of PCP produces long-lasting alterations in the locomotor response to a PCP and MK-801 challenge. These alterations might be indicative of residual PCP-induced motor deficits. Supported by DA06319.
NBTS 32 WARD*, J.H., K.S. GRANT-WEBSTER, and T.M. BURBACHER, Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle Wa. The effects of in-utero methanol exposure on the development of visual acuitv in infant monkevs. Use of fuel additives without documentation of safety as in the case of lead have resulted in enormous public health consequences. The proposal to add methanol to gasoline or to design automobiles that use methanol as a primary fuel will necessarily widen consumer exposure to this material. The health effects that may be associated with increased environmental exposure to methanol are not well documented at this time. This study provides the f'n'st data on the functional consequences on visual acuity of in-utero exposure to methanol in nonhuman primate infants. Macaca fascicularis females were exposed to either 0 ppm, 200 ppm, 600 ppm or 1800 ppm methanol in air for 2 hours/day, 7 days/week prior to and during pregnancy. Infants were tested at 5 different ages from 1 to 16 weeks of age using black and white stripes of varying widths. The method of choice for assessing infant vision was the two alternative forced-choice preferential looking paradigm. To obtain visual acuity functions, a plot of observer performance versus stripe width is fitted with a curve and the threshold of visual acuity is determined. The performance data from the methanol exposed infants will be compared with the performance of the control subjects to determine whether in-utero methanol exposure is associated with changes in visual acuity. Supported by Grant #90-9 Health Effects Institute.
NBTS 33 GRANT-WEBSTER, K.S., N. A. LIBERATO, and T.M. BURBACHER, Dept. of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle, WA. The Neurobehaviorai Conseouences of InUtero Exuosure to Inhaled Methanol in Macac8 Fascicularis Infants.
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