title: Prenatal cocaine and/or nicotine exposure in rats: preliminary findings on long-term cognitive outcome and genital development at birth.
abstract: Prenatal cocaine or nicotine exposure is associated with a variety of teratogenic effects. The current study was conducted to determine their effects alone and in combination on cognitive function and sexual differentiation. Pregnant Long-Evans rats (N = 19) were exposed to either cocaine (15 mg/kg/dose b.i.d. SC on GD 8-20); nicotine (4 mg/kg/day continuous SC infusion on GD 4-20); both nicotine + cocaine; or vehicle only. Birth weight and anogenital distance (AGD) were measured in all pups at birth. Learning and memory were tested in the Morris water maze (MWM) during prepubertal and pubertal ages in five daily consecutive sessions and a sixth session 1 week later and in the radial-arm maze (RAM) during adulthood. In the RAM, a drug challenge of the beta-noradrenergic antagonist propranolol (10-20 mg/kg) was given after acquisition training. Maternal weight gain was reduced 13-42% and offspring birth weight was reduced by 7-12% in all three exposure groups compared to controls. Cocaine decreased the AGD of males (2.68 mm) compared to 2.88 mm in noncocaine-exposed male pups (p < 0.025). A sex-selective cocaine effect was also seen after adjustment of AGD measurements for body weight. With this measure cocaine-treated females showed significantly (p < 0.05) greater AGD than those not exposed to cocaine. In the MWM, there were two types of trials: cued reference memory trials and uncued spatial working memory trials. On cued reference memory trials significant cocaine-induced latency deficits were seen on only the first session. On spatial working memory trials cocaine-induced latency deficits were seen throughout daily training on sessions 1-5, but not the retention session 6, 1 week later. During RAM acquisition, there were no significant differences in choice accuracy between exposure groups. Following propranolol challenge, deficits in choice accuracy were demonstrated in rats prenatally exposed to cocaine or nicotine. These rats did not show any response to propranolol, whereas the controls slightly improved their choice accuracy. The results of this study indicated that prenatal cocaine exposure altered long-term cognitive function under basal conditions in the MWM and drug challenge in the RAM, birth weight, and genital development. Cocaine-induced cognitive deficits were predominately in working memory rather than reference memory or long-term retention. Prenatal nicotine exposure was only observed to alter birth weight and cognitive function in response to propranolol challenge in the RAM.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Cutler
authors.forename: A E
authors.initials: AE
authors.lastname: Wilkerson
authors.forename: J L
authors.initials: JL
authors.lastname: Gingras
authors.forename: E D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000014:Abnormalities, Drug-Induced; D000375:Aging; D001003:Anal Canal / Q000033:anatomy & histology; D000704:Analysis of Variance; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects*; D005260:Female; D008098:Litter Size; D008297:Male; D018782:Maze Learning; D008568:Memory; D009538:Nicotine / Q000633:toxicity*; D010413:Penis / Q000033:anatomy & histology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012733:Sex Differentiation; D012744:Sex Ratio; D012741:Sexual Maturation; D013723:Teratogens / Q000633:toxicity; D014621:Vagina / Q000033:anatomy & histology
chemical_list: D013723:Teratogens; D009538:Nicotine; D011433:Propranolol; D003042:Cocaine