Pregnant rats were treated either throughout gestation (GD 1-20) with 30 mg/kg per day (chronic cocaine) or with one 15-mg/kg dose immediately following parturition (acute cocaine). Chronic and acute cocaine treatment delayed or diminished the postpartum onset of some components of maternal behavior, and chronically treated dams were significantly more aggressive toward a male intruder than acute cocaine-treated or saline-treated dams. Cocaine increased the latency to crouch over pups and decreased crouch duration during a 30-min observation period that immediately followed parturition. Latencies to nest build were also longer in more chronic cocaine-treated dams than in saline controls. On Day 6 postpartum, 83% of chronic cocaine-treated dams pinned and attacked an intruder male 8 or more times during a 10-min observation period, whereas only 4% of acute cocaine-treated and none of the saline-treated dams exhibited this much aggression.

Maternal cocaine abuse during pregnancy has been correlated with a greater incidence of maternal neglect and problems with maternal-infant bonding. 1 Children of mothers who have abused cocaine during pregnancy have exhibited signs of increased irritability and altered state liability as newborns 2,3 and are aggressive, show poor social attachment, and display abnormal play behavior in unstructured environments as young children. 4 These data suggest cocaine-induced, abnormal development of socioemotional behavior, but it is difficult to determine if these deficits are a direct result of cocaine or are related to living in an unstable or abusive environment.Animal research on the effects of prenatal cocaine exposure suggest that offspring exposed prenatally to cocaine exhibit signs of behavioral abnormalities including increased "emotionality" and neophobia 5,6 and aggression towards an intruder or other untreated conspecifics. 7-9 Long-term changes in specific neurotransmitter systems may be related to behavioral alterations.On the basis of previous findings, 7-9 we focused our research on cocaine-induced alterations of both maternal and offspring social/aggressive behavior. The following data include a summary of results from several recent experiments.a These studies were supported in part by the National Institute on Drug Abuse Grant R29-DA08456-01 (to J.M.J.) and the UNC METHODS Treatment GroupsDams received 15 mg/kg of cocaine-HCL (Sigma Chemical Co., St. Louis, Missouri) in a saline solution (CC) or an equal volume of (0.9%) normal saline (Sal) twice daily at approximately 9:00 AM and 4:00 PM from gestational days 1-20. An intermittent cocaine group received the same dose of cocaine on 2 consecutive days every 4 days throughout gestation (days 2-3, 8-9,14-15, and 19-20), and the amfonelic acid-treated (AFA, a selective dopamine uptake inhibitor) dams received 1.5 mg/kg of AFA dissolved in a pH 10 solution (Sterling Winthrop Labs, Rensselaer, New York) once daily (9:00 AM) on gestational days 1-20. ProcedureTreatment dams were either yoke fed or fed ad libitum, were weighed daily, and had their daily food consumption measured. Dams were tested on postpartum days 6, 8, and 10 for aggression towards an intruder during a 10-minute period. On postpartum days 8 or 11, dams were killed and the ventral tegmental area, hippocampus, and amygdala were removed for oxytocin radioimmunoassay. Details of aggression testing procedures were published elsewhere. 10 Pups were placed with surrogates immediately after birth, weaned at 21 days of age, and separated into same sex groups of three for behavioral testing on postnatal days 30, 60, 90, and 180. Pups from three of the test periods (30, 60, and 180 days) were used for HPLC analyses of monoamines, and several pups were killed on postnatal days 1, 4, and 10 for assessment of 5-HT 1A receptor development using immunobinding assays (using a specific 5-HT 1A antipeptide antibody, which was a gift of John Raymond) and quantitative, competitive RT-PCR using internal standar...

Pregnant rats were treated with 30 mg/kg per day cocaine or normal saline either throughout gestation (GD 1–20, cocaine and saline withdrawal) or throughout gestation and continuing into lactation for 10 days postpartum (cocaine and saline nonwithdrawal). All cocaine-treated dams exhibited more disruptions in the onset of maternal behavior (retrieval, licking, crouching) and were more aggressive (threats and attacks) towards an intruder on postpartum day 6 than saline-treated dams. There were no significant differences in these behaviors between withdrawn and nonwithdrawn cocaine-treated dams. These findings indicate that changes in maternal behavior following chronic moderate cocaine treatment are not simply the result of withdrawal from cocaine treatment following gestation and that other possible mechanisms should be examined.

Children prenatally exposed to cocaine are reported to exhibit inappropriate social behavior, including aggression. We have recently observed a similar phenomenon in rats prenatally exposed to cocaine. Pregnant females were injected twice daily with 15 mg/kg cocaine hydrochloride or saline on gestation days l-20. Offspring were tested for social behavior towards two unfamiliar, untreated rats of the same age and sex. Cocaine-treated males (90 PND) took longer to reciprocate contact and cocaine-treated females (60 PND) spent more time rough grooming unfamiliar females. Male cocaine offspring (180 PND) tested for aggression exhibited an increased frequency and duration and decreased latency to chase an intruder. ACTH was lower in cocaine-treated males (150-180 PND) following plus-maze exposure or exposure to an unfamiliar male. Our data indicate that prenatal cocaine treatment in rats increases fear or aggression responses, dependent on sex and stimulus situation. KeywordsCocaine; Prenatal; Development; Social behavior; Aggression; ACTH; HPA axisThe Alarming rise of cocaine abuse among pregnant women has promoted much concern over the potential behavioral effects on prenatally exposed neonates and infants (4,20). Offspring of mothers that have abused cocaine during pregnancy have exhibited signs of increased irritability and altered state lability as newborns (2,3). Research has also shown that young children prenatally exposed to cocaine are somewhat aggressive, show poor social attachment, and display abnormal play behavior in unstructured environments (7,18). These data are suggestive of a cocaine-induced, abnormal development of socioemotional behavior. However, mothers who have abused cocaine during pregnancy have been shown to bond poorly to their infants (1), making it difficult to determine if the origin of these deficits occur as a direct result of cocaine acting on the developing fetus, being raised in an unstable or abusive environment in which parental drug abuse may be prevalent, or a combination thereof.Recent animal research on the effects of prenatal cocaine exposure has begun to focus on behaviors that appear to be similar to the behaviors exhibited by human offspring prenatally exposed to cocaine. Rodent studies suggest that offspring exposed prenatally to cocaine exhibit signs of behavioral abnormalities including increased "emotionality" and neophobia (5,8), and aggression towards an intruder (9). Though these studies employed cross-fostered Copyright © 1995 offspring, another recent study found that untreated offspring fostered to cocaine-treated mothers also displayed higher levels of shock-elicited aggression (6), suggesting a possible postnatal environmental influence.Based on the previous findings of abnormal behavioral responses of fear and aggression in male rats upon reaching puberty or adulthood, respectively (8,9), the present study was undertaken to determine if these kinds of behaviors changes were task or sex related. We hypothesized that the appearance of the behaviors w...

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