Neurotoxicology and teratology
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Neurotoxicol Teratol · Jan 2000
Comparative StudyAdaptation of a primate operant test battery to the rat: effects of chlorpromazine.
The National Center for Toxicological Research (NCTR) Operant Test Battery (OTB) has been used extensively in rhesus monkeys to characterize the effects of drugs and toxicants on the performance of tasks designed to model several cognitive functions. Recently, the majority of the OTB tasks have been adapted for use in rats. The current study is the first to examine the effects of a prototypic pharmacological agent previously assessed in monkeys on rat OTB performance. ⋯ This pattern of sensitivity was very similar to that obtained when chlorpromazine was tested in monkeys performing the OTB. These data thus suggest that operant tasks designed to model cognitive functions in monkeys can also be used in rats, and that the effects of chlorpromazine on the performance of these tasks may be predictive of results obtained with monkeys. Further characterization of the rat OTB using prototypic pharmacological agents will further determine the extent to which drug effects on rat OTB performance can be generalized to primates.
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Neurotoxicol Teratol · Mar 2004
Comparative StudyGestational exposure to methylmercury retards choice in transition in aging rats.
Developmental exposure to methylmercury has behavioral effects that extend into adulthood and aging. In this study, methylmercury's prolonged effects on the acquisition of choice and sensitivity to changes in reinforcement rates were studied. Pregnant female rats were exposed to drinking water containing 0, 0.5, or 6.4 ppm Hg as methylmercury, resulting in about 40 and 500 microg/kg/day of mercury intake. ⋯ Moreover, two rate measures, lever-press rates and changeover rates, were not systematically affected by methylmercury. The acquisition of choice appears to be very sensitive to subtle consequences of developmental methylmercury exposure. The specific tactics greatly reduced the time required to study behavior in transition from a month in previous reports to a single session here.
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Neurotoxicol Teratol · Jan 2004
Comparative StudyPerinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats.
Children exposed to alcohol prenatally suffer from a variety of behavioral alterations, including hyperactivity and learning deficits. Given that women continue to drink alcohol during pregnancy, it is critical that effective interventions and treatments be identified. Previously, we reported that early postnatal choline supplementation can reduce the severity of learning deficits in rats exposed to alcohol prenatally. ⋯ Exposure to choline significantly reduced the number of ethanol-related errors. Importantly, these behavioral changes were not due to the acute effects of choline, but were related to long-lasting organizational effects of early choline supplementation. These data suggest that early dietary interventions may reduce the severity of fetal alcohol effects.
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Neurotoxicol Teratol · Mar 2007
Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats.
This study evaluated the efficacy of a 3-week course of succimer treatment to alleviate behavioral deficits in rats exposed to lead (Pb) for the first 4 weeks of life. A 3 x 2 factorial design was used: three levels of lead exposure (No Pb, Moderate, and High Pb) and two levels of chelation (succimer or vehicle). Behavioral testing was conducted following chelation therapy, from 2 to 9 months of age; this report presents the results of two of the administered tasks: (1) a conditional olfactory discrimination task (baseline task), and (2) a conditional olfactory discrimination task with periodic reward omission on some correct trials (RO task). ⋯ Importantly, succimer treatment was effective in normalizing the heightened reactivity of the lead-exposed animals to both errors and reward omission. In addition, non-lead-exposed rats that were treated with succimer tended to be more affected by a prior error than controls in their latency to respond on post-error trials. In sum, these findings provide new evidence that succimer chelation can significantly lessen the lasting neurobehavioral dysfunction produced by early lead exposure, but also suggest that there may be risks of administering the drug to individuals without elevated blood lead levels.
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Neurotoxicol Teratol · May 2000
Comparative StudyThe influence of route of administration on the acute cardiovascular effects of cocaine in conscious unrestrained pregnant rats.
The intravenous route of administration, accessed via a subcutaneous vascular access port, has been recently suggested as an animal model for studying the developmental effects of maternal cocaine abuse in the pregnant and/or group-housed rat. The present study (1) assessed the cardiovascular effects of intravenous (IV) cocaine, delivered via bolus injection, in chronically catheterized near-term pregnant rats, and (2) compared the IV cardiovascular responses to those following cocaine delivered via the commonly employed subcutaneous (SC) and intragastric (IG) routes of administration. Pregnant gestation day 15 (GD15) young adult female Sprague-Dawley rats (n = 21) were anesthetized and catheters surgically implanted into the carotid artery, jugular vein, fundus of the stomach, and a subcutaneous pouch. ⋯ Finally, the pressor effects of IV cocaine paralleled the rapidly peaking arterial plasma levels of cocaine noted within 30 s after the initiation of drug injection. In sum, prominent effects of IV cocaine on maternal cardiovascular physiology are noted; as such, the recent reports of a lack of maternal/fetal toxicity following daily (3-6mg/kg) IV cocaine during GD8-21 are not due to use of an ineffective drug dose. It was equally clear that the SC and IG routes of exposure did not reproduce the cardiovascular component(s) of the expected physiological response to cocaine.