Elsevier

Neurotoxicology and Teratology

Volume 21, Issue 5, September–October 1999, Pages 539-550
Neurotoxicology and Teratology

Articles
Prenatal Intravenous Cocaine Adversely Affects Attentional Processing in Preweanling Rats

https://doi.org/10.1016/S0892-0362(99)00024-0Get rights and content

Abstract

Perhaps the sole, clinically reported, deficit in infants of women that abused cocaine (COC) during pregnancy that persists through early childhood is that of an attentional disorder. Using the heart rate orienting response (HR-OR), a putative valid and reliable measure of attention, we examined the offspring of rats exposed to COC in utero via the clinically relevant intravenous (IV) route. Sprague–Dawley females, implanted with IV access ports prior to breeding, were administered saline or 3 mg/kg COC HCl, 1×/day on gestational day (GD) 8–14 and 2×/day on GD15–21. No significant effects of prenatal COC were apparent for maternal or litter parameters. Six pups/litter were tested: one of each sex on postnatal day (PD) 12, PD16, and PD21. Following 20 min of adaptation, pups were exposed to a novel odor (20 s amyl acetate) for a set of four acquisition trials; after a 4-h retention interval, the same procedure was again employed. At PD12, both prenatal COC and control pups demonstrated a significant HR-OR on the acquisition trials and both groups showed significant within-session habituation. Across the 4-h retention interval, prenatal COC-exposed pups showed habituation whereas control pups did not. At PD16, the magnitude of the HR-OR was significantly greater in prenatal COC-exposed pups relative to control pups. Within-session habituation also characterized the HR-OR of the COC, but not control, pups. For the retention data, within-subject and regression analyses suggested the COC-exposed pups displayed greater between and within-session habituation, respectively. At PD21, the prenatal COC-treated pups displayed an HR-OR that did not habituate across acquisition trials; the control pups displayed a significant HR-OR only during the initial 5 s of the first two trials. During the retention trials, regression analyses again suggested the COC-exposed pups displayed greater evidence of within-session habituation. Collectively, these data demonstrate that prenatal exposure to COC alters attention throughout the preweanling period of development. Given the putative role of norepinephrine, but not dopamine or serotonin, in central mediation of the HR-OR of preweanling rats, the effects of prenatal IV COC exposure in this task are consistent with a noradrenergically based attentional disorder.

Section snippets

Animals

Nulliparous female Sprague–Dawley rats were obtained from Harlan Sprague–Dawley, Inc. (Indianapolis, IN) at approximately 10–12 weeks of age (225–249 g), placed into quarantine for 1 week, and subsequently moved to the animal colony. The animals were maintained according to NIH guidelines in AAALAC-accredited facilities. Food (Pro-Lab Rat, Mouse, Hamster Chow No. 3000, Cincinnati Lab Supply, Cincinnati, OH) and water were available ad libitum. The animal facility was maintained at 21°C ± 2°C,

Results

Gestational weight gain of the dams was not significantly affected by IV injections of cocaine during the last 2 weeks of pregnancy (Table 1). The analysis of percentage weekly weight gain failed to detect any significant effect of the prenatal cocaine exposure and also failed to detect any effect of the catheterization, daily injection, and handling. The analysis of mean total gestational weight gain (Table 2) similarly failed to find any significant effects of prenatal cocaine exposure or the

Discussion

Administration of cocaine to pregnant rats by a clinically relevant route (IV) exerted an adverse effect on attentional processes in the offspring. The major effects on the HR-OR were fourfold: 1) Elicitation of the HR-OR was significantly greater in prenatal cocaine-exposed pups relative to controls on PD16 and 21, but not on PD12; 2) within-session habituation was noted in prenatal cocaine-exposed pups, but not control pups, during the acquisition trial series on PD16 (habituation was neither

Acknowledgements

This work was supported, in part, by grants from the University of Kentucky Medical Center Research Fund, the Tobacco and Health Research Institute, and the National Institutes of Health (National Institute on Drug Abuse, DA09160, DA11337, and DA06638; National Institute of Environmental Health Sciences, ES06259). The Tobacco and Health Research Institute (THRI) is an administrative unit of the University of Kentucky and is not affiliated with the Tobacco Research Council nor does it receive

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