Linda R. Noonan

Effects of chronic and acute cocaine treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats

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.

Prenatal Cocaine Exposure Affects Social Behavior in Sprague-Dawley Rats

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 1-20. 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.

Chronic Cocaine Treatment Alters Social/Aggressive Behavior in Sprague-Dawley Rat Dams and in Their Prenatally Exposed Offspringa

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 newborns2,3 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 neophobia5,6 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.

Effects of Short- and Long-Term Withdrawal from Gestational Cocaine Treatment on Maternal Behavior and Aggression in Sprague-Dawley Rats

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 the 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.

Neonatal stress transiently alters the development of hippocampal oxytocin receptors

The development of brain oxytocin (OXT) receptors was examined following the mild stress of daily, 20 min separations of infant rats from their mothers (repeated separation condition) or in undisturbed controls. Changes in OXT receptors were characterized in cell membrane preparations, using the OXT receptor ligand [125I]d(CH2)5[Tyr(Me)2Thr4Tyr-NH9(2)]-ornithine vasotocin ([125I]OTA), from rats at 4, 8, 14, 22 postnatal days of age or as adults. In the hippocampus of control animals, [125I]OTA binding was highest at day 4 or 8 and declined thereafter. Repeated separation decreased the Bmax of [125I]OTA binding in whole hippocampus at day 8, an effect that did not persist into adulthood. This effect was found to be confined to the rapidly proliferating, dorsal hippocampus. It has been suggested that brain OXT is involved in both affiliative/social and stress-related behaviors. While the specific function of OXT receptors in hippocampus is currently unknown, mild stress to the infant and the disruption of infant-mother contact transiently alters the normal development of this system.

Neonatal administration of oxytocin increases novelty-induced grooming in the adult rat

Three-day-old Sprague-Dawley rat pups were intracisternally infused with a single dose of oxytocin (1 microgram/2 microliters) or saline, or were untreated. As adults, these animals were observed for novelty-induced grooming, analgesia measured by the hot-plate test, and behavior in the open field. Oxytocin treatment during infancy resulted in an elevation of novelty-induced grooming when compared to saline and untreated animals. There were no significant oxytocin treatment effects on analgesia response or open-field behaviors. Oxytocin given early in life may have permanent effects on certain behavioral responses to stress.

Effects of thyroid state on preference for and sensitivity to ethanol in Fischer-344 rats.

1. It has been reported by several groups that thyroid status can alter ethanol preference in rats. However, results using different methods and different strains of rats have not been consistent. 2. In this study, thyroidectomy or T4 augmentation was used to produce hypothyroidism or hyperthyroidism, respectively, in adult male Fischer-344 rats. 3. Preference for weak solutions (4 or 5%) of ethanol or tap water and ethanol-induced sedation and hypothermia were compared in hypothyroid, hyperthyroid and euthyroid rats. 4. No significant differences in preference indices (the ratios of ethanol to total liquid consumed) among the three groups were observed; however, for ethanol to contribute a greater portion of total calories ingested by hypothyroid rats than by euthyroid or hyperthyroid rats. 5. The duration of sleep resulting from a single i.p. injection of 2.5 mg/kg ethanol was increased (by 34%) in hyperthyroid rats and decreased (by 16%) in hypothyroid rats compared to euthyroid controls. Only the effect of hyperthyroidism was significant at the 0.05 level. 6. Colonic temperatures differed with thyroid state (hyperthyroid > euthyroid > hypothyroid) but the decrease produced by ethanol did not differ by thyroid state. 7. Observed differences in ethanol-induced sedation are consistent with differences in brain TRH levels and effects on neurotransmitter systems associated with different thyroid states.