Role of Rodent Vocalizations in Cocaine-Induced Maternal Neglect

A greater incidence of maternal neglect, problems with mother-infant bonding, child abuse, and placement in foster homes has been correlated with maternal cocaine use during pregnancy compared to mothers with no gestational cocaine use. Infants exposed to cocaine during pregnancy show many signs, particularly early in the postnatal period, of poor state control including: irregular crying behavior, and extreme state liability. To date little evidence has been published of how cocaine decreases both maternal perception of infant care needs and infant elicitation of maternal response. Using an animal model of cocaine-induced maternal neglect the aim of this dissertation is to: 1) record and quantify differences following prenatal cocaine exposure in infant rat vocalizations, a known stimulus of rodent maternal behavior; 2) test whether gestational cocaine treatment decreases maternal preference-like behavior for recorded vocalizations from prenatal cocaine-exposed infant rats; and 3) determine if any identified cocaine-induced decreases in maternal proximity preference for infant rat vocalization recordings correlate with maternal neurobiological differences in oxytocin, cFos and FosB protein expression. The data presented in this dissertation demonstrate that cocaine-treatment during gestation alters infant rat vocalization characteristics, decreases maternal preference for prenatal cocaine-exposed infant rat vocalization recordings, and that oxytocin expression in the medial preoptic area is decreased in cocaine-treated rat mothers that choose to spend less time in close proximity to recordings of prenatal cocaine-exposed infant rat vocalizations. Ultimately these data provide justification for continued work to explore the separate and interactive factors influencing maternal behavior and within this theoretical framework to drive development of both behavioral and pharmacotherapeutic interventions for the treatment of maternal neglect.Doctor of Philosoph

Combined Norepinephrine/Serotonergic Reuptake Inhibition: Effects on Maternal Behavior, Aggression, and Oxytocin in the Rat

Background: Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior (MB), although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent MB in rodents indicated significant alterations in postpartum maternal care, aggression, and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on MB, aggression, and oxytocin system changes. Methods: Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. MB and postpartum aggression were assessed on postpartum days 1 and 6 respectively. Oxytocin levels were measured in relevant brain regions on postpartum day 7. Predictions were that amitriptyline would decrease MB and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression. Results: Amitriptyline and desipramine differentially reduced MB, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in maternal care