TY - JOUR
T1 - Perinatal methanol exposure in the rat II. Behavioral effects in neonates and adults
AU - Stern, Sander
AU - Cox, Christopher
AU - Preston, Ray
AU - Sharma, Archana
AU - Inglis, Geoffrey B.
AU - Balys, Marlene
AU - Weiss, Bernard
N1 - Funding Information:
Funding for this work was provided in part by Agreement 90-8 from the Health Effects Institute, B. Weiss, Principal Investigator, and by NIEHS Center Grant ES-01247.
PY - 1997/4
Y1 - 1997/4
N2 - The use of methanol as a component of automobile fuel will increase perinatal exposures in the general population. Few studies have addressed questions concerning neurotoxicity stemming from such exposures. In the current study, four cohorts of pregnant Long-Evans rats, each cohort consisting of an exposure and a control group, were exposed to 4500 ppm methanol vapor in Rochester-type inhalation chambers for 6 hr daily beginning on Gestation Day 6. Exposure continued for both dams and pups through Postnatal Day 21 (PND 21) to model gestational and neonatal toxicity in humans. Several behavioral procedures were used to assess exposure effects in the offspring. Male-female littermates were studied whenever possible to examine sex differences, with one pair from a litter for each procedure. Exposure to methanol did not affect suckling latency and nipple attachment on PND 5 or performance on an aversive olfactory conditioning procedure on PMD 10. Exposure to methanol did alter performances in a motor activity procedure. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control group pups. Two operant conditioning procedures, not used previously in this context, assayed other littermates as adults. A fixed ratio schedule required the rat to rotate a running wheel a specified number of revolutions to obtain food-pellet reinforcers. When the fixed ratio requirement changed, number of responses (revolutions) per 1-hr session displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. Compared to initial baseline performances, methanol-exposed males showed decreases, and methanol-exposed females increases, in the rate of running. A stochastic spatial discrimination procedure permitted subjects to respond on any three levers, with the probabilities of food-pellet delivery determined by the location of the preceding response. A reinforcement matrix defined the response sequence required to maximize reinforcements. When the matrix was changed, the methanol-exposed subjects responded less efficiently at asymptotic levels of performance than controls. Across procedures, developmental exposure to 4500 ppm methanol vapor was associated with subtle behavioral changes in both neonates and adults.
AB - The use of methanol as a component of automobile fuel will increase perinatal exposures in the general population. Few studies have addressed questions concerning neurotoxicity stemming from such exposures. In the current study, four cohorts of pregnant Long-Evans rats, each cohort consisting of an exposure and a control group, were exposed to 4500 ppm methanol vapor in Rochester-type inhalation chambers for 6 hr daily beginning on Gestation Day 6. Exposure continued for both dams and pups through Postnatal Day 21 (PND 21) to model gestational and neonatal toxicity in humans. Several behavioral procedures were used to assess exposure effects in the offspring. Male-female littermates were studied whenever possible to examine sex differences, with one pair from a litter for each procedure. Exposure to methanol did not affect suckling latency and nipple attachment on PND 5 or performance on an aversive olfactory conditioning procedure on PMD 10. Exposure to methanol did alter performances in a motor activity procedure. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control group pups. Two operant conditioning procedures, not used previously in this context, assayed other littermates as adults. A fixed ratio schedule required the rat to rotate a running wheel a specified number of revolutions to obtain food-pellet reinforcers. When the fixed ratio requirement changed, number of responses (revolutions) per 1-hr session displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. Compared to initial baseline performances, methanol-exposed males showed decreases, and methanol-exposed females increases, in the rate of running. A stochastic spatial discrimination procedure permitted subjects to respond on any three levers, with the probabilities of food-pellet delivery determined by the location of the preceding response. A reinforcement matrix defined the response sequence required to maximize reinforcements. When the matrix was changed, the methanol-exposed subjects responded less efficiently at asymptotic levels of performance than controls. Across procedures, developmental exposure to 4500 ppm methanol vapor was associated with subtle behavioral changes in both neonates and adults.
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U2 - 10.1006/faat.1997.2288
DO - 10.1006/faat.1997.2288
M3 - Article
C2 - 9143486
AN - SCOPUS:26844573068
SN - 0272-0590
VL - 36
SP - 163
EP - 176
JO - Fundamental and Applied Toxicology
JF - Fundamental and Applied Toxicology
IS - 2
ER -