The link between impaired maternal behavior (MB) and cocaine treatment could result from druginduced decreases in maternal reactivity to offspring, prenatal drug exposure (PDE) in offspring that could alter their ability to elicit MB, or the interaction of both, which could subsequently impair MB of the 1st-generation dams. Following chronic or intermittent cocaine or saline treatment during gestation, rat dams rearing natural or cross-fostered litters were compared along with untreated dams for MB. Untreated 1st-generation females with differentially treated rearing dams and PDE were tested for MB with their natural litters. The authors report disruptions in MB in dams and their 1st-generation offspring, attributable to main and interaction effects of maternal treatment, litter PDE, and rearing experience. Pregnant women who use cocaine perpetrate child abuse and neglect more often than women who do not use cocaine during pregnancy (Hawley, Halle, Drasin, & Thomas, 1995; Tyler, Howard, Espinosa, & Doakes, 1997; Wasserman & Leventhal, 1993). Maternal cocaine abuse during pregnancy has also been strongly associated with deficits in maternalinfant bonding (Burns, Chethik, Burns, & Clark, 1991), and mothers with a history of substance abuse often exhibit poor mother-infant interactions (Bauman & Dougherty, 1983;Bays, 1990; Howard, Beck-with, Espinosa, & Tyler, 1995;Johnson & Rosen, 1990). Though studies with human participants are helpful in understanding the connection between cocaine use and maternal neglect, these experiments are correlational. There is a necessary lack of control over many important variables that could confound the results, such as socioeconomic issues, lack of family support, multidrug abuse, and poor general prenatal care (Chasnoff et al., 1998;Koren et al., 1998). Studies that use numerous controls have shown a strong correlation between reported history of child maltreatment and the perpetration of maltreatment and/or neglect in next-generation mothers (Egeland, Jacobvitz, & Papatola, 1987;Hunter, Kilstrom, Kraybill, & Loda, 1978).In order to appropriately investigate and describe the characteristics of cocaine-induced disruption of maternal behavior and potential neglect, as well as possible intergenerational effects of such disruptions, a nonhuman cocaine abuse model offers several advantages. The laboratory rat is a particularly good model for the study of maternal behavior. Their offspring are born blind, unable to thermoregulate, defecate, urinate, or protect themselves from attack (Numan, 1994), thus needing considerable maternal care to survive (Stern, 1997). Behaviorally and neurologically, maternal behavior in the rat has also been relatively well characterized (Numan, 1994;Pedersen, Ascher, Monroe, & Prange, 1982;Pedersen, Caldwell, Walker, Ayers, & Mason, 1994) so that any insult to normal maternal behavior can be easily determined.Maternal separation studies also support a rat intergenerational model of behavior showing that cross-fostering results in behavior of offsp...

Studies using dopaminergic and serotonergic agonists or antagonists implicate involvement of these systems in various aspects of early maternal behavior and postpartum aggression towards an intruder in rats, both of which are associated with the presence of oxytocin in specific brain regions. It is unclear however, if or how long-term uptake inhibition of either neurotransmitter system alone or in combination, affects oxytocin system dynamics or maternal behavior/ aggression. Pregnant women frequently take drugs (antidepressants, cocaine) that induce longterm reuptake inhibition of dopamine and/or serotonin, thus it is important to understand these effects on behavior and biochemistry. Rat dams were treated throughout gestation with amfonelic acid, fluoxetine, or a combination of both, to investigate effects of reuptake inhibition of dopamine and serotonin systems respectively, on maternal behavior, aggression and oxytocin. The more appetitive aspects of maternal behavior (nesting, licking, touching) and activity were increased by the low dose of amfonelic acid, high dose of fluoxetine, or the high dose combination more than other treatments. Aggression was decreased by amfonelic acid and somewhat increased by fluoxetine. Dopamine uptake inhibition appears to have a strong effect on hippocampal oxytocin levels, while receptor dynamics may be more strongly affected by serotonin uptake inhibition.

Gestational cocaine treatment results in significantly increased maternal aggression towards an intruder by postpartum day six, while acute postpartum treatment dose dependently decreases maternal aggressive (MA) behavior. Both increased and decreased aggression in the cocainetreated dams are correlated with either decreased or increased levels of oxytocin in the amygdala, respectively. The current study was an effort to determine whether the effect of gestational cocaine on maternal aggression is transient or would continue into the postpartum period; whether an intermittent cocaine treatment regimen, which incorporates gestational and postpartum intermittent cocaine treatment, would differ from chronic daily gestational treatment; and finally, whether next generation female offspring of cocaine-treated or control dams would have altered MA behavior and oxytocin system changes attributable to either prenatal drug exposure, rearing condition or both. We now report no increase in maternal aggression following chronic gestational treatment and significantly lower levels of aggression in intermittently treated dams on postpartum day eight, with no significant effects in either group on postpartum day 12. Young adult female offspring of the cocaine-treated and control dams, who reared their own natural litters and were tested on postpartum day eight for maternal aggression, had higher levels of maternal aggression towards an intruder attributable to both prenatal cocaine exposure and rearing condition. Higher aggression in cocaine-reared next generation dams was associated with lower levels of oxytocin in the amygdala. Intergenerational effects of cocaine were apparent with respect to aggression and oxytocin system changes.

Maternal presence has a potent buffering effect on infant fear and stress responses in primates. We previously reported that maternal presence is not effective in buffering the endocrine stress response in infant rhesus monkeys reared by maltreating mothers. We have also reported that maltreating mothers show low maternal responsiveness and permissiveness/secure-base behavior. Although still not understood, it is possible that this maternal buffering effect is mediated, at least partially, through deactivation of amygdala response circuits when mothers are present. Here we studied rhesus monkey infants that differed in the quality of early maternal care to investigate how this early experience modulated maternal buffering effects on behavioral responses to novelty during the weaning period. We also examined the relationship between these behavioral responses and structural connectivity in one of the underlying regulatory neural circuits: amygdala-prefrontal pathways. Our findings suggest that infant exploration in a novel situation is predicted by maternal responsiveness and structural integrity of amygdala-prefrontal white matter depending on maternal presence (positive relationships when mother is absent). These results provide evidence that maternal buffering of infant behavioral inhibition is dependent on the quality of maternal care and structural connectivity of neural pathways that are sensitive to early life stress.

The purpose of this article is to describe the development of translational methods by which spectrum analysis of human infant crying and rat pup ultrasonic vocalizations (USVs) can be used to assess potentially adverse effects of various prenatal conditions on early neurobehavioral development. The study of human infant crying has resulted in a rich set of measures that has long been used to assess early neurobehavioral insult due to non-optimal prenatal environments, even among seemingly healthy newborn and young infants. In another domain of study, the analysis of rat put USVs has been conducted via paradigms that allow for better experimental control over correlated prenatal conditions that may confound findings and conclusions regarding the effects of specific prenatal experiences. The development of translational methods by which cry vocalizations of both species can be analyzed may provide the opportunity for findings from the two approaches of inquiry to inform one another through their respective strengths. To this end, we present an enhanced taxonomy of a novel set of common measures of cry vocalizations of both human infants and rat pups based on a conceptual framework that emphasizes infant crying as a graded and dynamic acoustic signal. This set includes latency to vocalization onset, duration and repetition rate of expiratory components, duration of inter-vocalization-intervals and spectral features of the sound, including the frequency and amplitude of the fundamental and dominant frequencies. We also present a new set of classifications of rat pup USV waveforms that include qualitative shifts in fundamental frequency, similar to the presence of qualitative shifts in fundamental frequency that have previously been related to insults to neurobehavioral integrity in human infants. Challenges to the development of translational analyses, including the use of different terminologies, methods of recording, and spectral analyses are discussed, as well as descriptions of automated processes, software solutions, and pitfalls.