Prenatal intravenous cocaine adversely affects attentional processing in preweanling rats

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 HC1, 1X/day on gestational day (GD) 8-14 and 2X/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.