Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect.

Maternal behavior (MB) is a complex response to infant cues, orchestrated by postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB, little is known about real-time dopamine fluctuations during the postpartum period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine transients in the nucleus accumbens of early postpartum rats and compared them with dopamine transients in virgins and in postpartum females exposed to cocaine during pregnancy, which is known to disrupt MB. We hypothesized that dopamine transients are normally enhanced postpartum and support MB. In anesthetized rats, electrically evoked dopamine release was larger and clearance was faster in postpartum females than in virgins and gestational cocaine exposure blocked the change in clearance. In awake rats, control mothers showed more dopamine transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli may contribute toward differences in maternal phasic dopamine by evoking dopamine transients; supporting the feasibility of this hypothesis, urine composition (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed infants. These data, resulting from the novel application of fast-scan cyclic voltammetry to models of MB, support the hypothesis that phasic dopamine signaling is enhanced postpartum. Future studies with additional controls can delineate which aspects of gestational cocaine reduce dopamine clearance and transient frequency.

Effects of prenatal cocaine exposure on early postnatal rodent brain structure and diffusion properties.

Prenatal cocaine exposure has been associated with numerous behavioral phenotypes in clinical populations, including impulsivity, reduced attention, alterations in social behaviors, and delayed language and sensory-motor development. Detecting associated changes in brain structure in these populations has proven difficult, and results have been inconclusive and inconsistent. Due to their more controlled designs, animal models may shed light on the neuroanatomical changes caused by prenatal cocaine; however, to maximize clinical relevance, data must be carefully collected using translational methods. The goal of this study was two-fold: (1) to determine if prenatal cocaine alters developmental neuroanatomy using methods that are available to human researchers, specifically structural MRI and diffusion tensor imaging, and (2) to determine the feasibility of rodent in vivo neuroimaging for usage in longitudinal studies of developmental disorders. Cocaine-exposed (prenatal days 1-20, 30mg/kg/day) rat pups were sedated and imaged live using diffusion tensor imaging and postmortem (fixed) using magnetic resonance histology on postnatal day 14. Volume and diffusion properties in whole brain as well as specific regions of interest were then assessed from the resulting images. Whole brain analyses revealed that cocaine-exposed animals showed no change in whole brain volume. Additionally, we found alterations in fractional anisotropy across regions associated with reward processing and emotional regulation, especially in the thalamus and globus pallidus, as well as sex-dependent effects of cocaine in the right cortex. Reductions in fractional anisotropy were paired with reductions only in axial diffusivity, which preliminarily suggests that the changes observed here may be due to axonal damage, as opposed to reductions in myelination of the affected regions/pathways. Our data indicate that prenatal cocaine may target a number of developing brain structures but does not result in overt changes to brain volumes. These results highlight not only the brain alterations that result from prenatal cocaine but also the advancements in live imaging that allow longitudinal study designs in other models.

Translational analysis of effects of prenatal cocaine exposure on human infant cries and rat pup ultrasonic vocalizations.

Spectral and temporal features of human infant crying may detect neurobehavioral effects of prenatal cocaine exposure (PCE). Finding comparable measures of rodent ultrasonic vocalizations (USVs) would promote translational analyses by controlling the effects of correlated variables that confound human studies. To this end, two studies examined the sensitivity of similar acoustic structures in human infant and rat pup vocalizations to effects of PCE. In Study 1, cry sounds of 107 one month-old infants were spectrum analyzed to create a novel set of measures and to detect the presence of hyperphonation - a qualitative shift to an atypically high fundamental frequency (basic pitch) associated with neurobehavioral insult. Infants with PCE were compared to infants with prenatal polydrug-exposure (PPE) without cocaine and with infants in a standard comparison (SC) group with no prenatal drug exposure. In Study 2, USVs of 118 five day-old rat pups with either PCE, prenatal saline exposure or no prenatal exposures were spectrum analyzed to detect the presence of frequency shifts - acoustic features that have a frequency waveform similar to that of hyperphonation. Results of study 1 showed PCE had two sets of sex-dependent effects on human infants: PCE males had higher pitched cries with more dysphonation (turbulence); PCE females had longer pauses between fewer cry sounds that were of lower amplitude than comparison groups. PCE and PPE infants had more cries with hyperphonation than SC infants. In study 2, PCE pups had a greater percentage of USVs with shift in the acoustic structure than pups in the two control groups. As such, the novel measures of human infant crying and rat pup USVs were sensitive to effects of PCE. These studies provide the first known translational analysis of similar acoustic structures of vocalizations in two species to detect adverse effects of prenatal drug exposure.

Prenatal cocaine effects on brain structure in early infancy.

Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life.

Effect of prenatal cocaine on early postnatal thermoregulation and ultrasonic vocalization production.

Prenatal cocaine exposure can alter the postnatal care received by rat pups. Such effects could be caused in part by alterations in pup-produced stimuli that elicit early postnatal maternal care. Pup ultrasonic vocalizations are thought to be a particularly salient stimulus, and when paired with other cues, may elicit maternal attention. Cocaine is known to acutely alter thermoregulatory and cardiac function, thus prenatal cocaine may affect vocalizations through altering these functions. The data presented here determine the impact of full term prenatal cocaine exposure, saline exposure, or no exposure on thermogenic capacity, cardiac function, and the resulting ultrasonic vocalizations across the early postnatal period (days 1-5). Results indicated that while sharing many similar characteristics with saline-exposed and untreated animals, prenatal cocaine exposure was associated with specific alterations in vocalization characteristics on postnatal day 1 (PND 1), including call amplitude. Furthermore, numerous spectral parameters of their vocalizations were found altered on PND 3, including rate, call duration, and frequency, while no alterations were found on PND 5. Additionally, cocaine-exposed pups also showed a reduced thermoregulatory capacity compared to saline animals and reduced cardiac mass compared to untreated animals on PND 5. Together, these findings indicate that prenatal cocaine may be altering the elicitation of maternal care through its impact on vocalizations and thermoregulation, and suggests a potential mechanism for these effects through cocaine's impact on developing stress systems.

3-dimensional diffusion tensor imaging (DTI) atlas of the rat brain.

Anatomical atlases play an important role in the analysis of neuroimaging data in rodent neuroimaging studies. Having a high resolution, detailed atlas not only can expand understanding of rodent brain anatomy, but also enables automatic segmentation of new images, thus greatly increasing the efficiency of future analysis when applied to new data. These atlases can be used to analyze new scans of individual cases using a variety of automated segmentation methods. This project seeks to develop a set of detailed 3D anatomical atlases of the brain at postnatal day 5 (P5), 14 (P14), and adults (P72) in Sprague-Dawley rats. Our methods consisted of first creating a template image based on fixed scans of control rats, then manually segmenting various individual brain regions on the template. Using itk-SNAP software, subcortical and cortical regions, including both white matter and gray matter structures, were manually segmented in the axial, sagittal, and coronal planes. The P5, P14, and P72 atlases had 39, 45, and 29 regions segmented, respectively. These atlases have been made available to the broader research community.

The translational role of diffusion tensor image analysis in animal models of developmental pathologies.

Diffusion tensor magnetic resonance imaging (DTI) has proven itself a powerful technique for clinical investigation of the neurobiological targets and mechanisms underlying developmental pathologies. The success of DTI in clinical studies has demonstrated its great potential for understanding translational animal models of clinical disorders, and preclinical animal researchers are beginning to embrace this new technology to study developmental pathologies. In animal models, genetics can be effectively controlled, drugs consistently administered, subject compliance ensured, and image acquisition times dramatically increased to reduce between-subject variability and improve image quality. When pairing these strengths with the many positive attributes of DTI, such as the ability to investigate microstructural brain organization and connectivity, it becomes possible to delve deeper into the study of both normal and abnormal development. The purpose of this review is to provide new preclinical investigators with an introductory source of information about the analysis of data resulting from small animal DTI studies to facilitate the translation of these studies to clinical data. In addition to an in-depth review of translational analysis techniques, we present a number of relevant clinical and animal studies using DTI to investigate developmental insults in order to further illustrate techniques and to highlight where small animal DTI could potentially provide a wealth of translational data to inform clinical researchers.

Development of translational methods in spectral analysis of human infant crying and rat pup ultrasonic vocalizations for early neurobehavioral assessment.

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.

Synergy of image analysis for animal and human neuroimaging supports translational research on drug abuse.

The use of structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) in animal models of neuropathology is of increasing interest to the neuroscience community. In this work, we present our approach to create optimal translational studies that include both animal and human neuroimaging data within the frameworks of a study of post-natal neuro-development in intra-uterine cocaine-exposure. We propose the use of non-invasive neuroimaging to study developmental brain structural and white matter pathway abnormalities via sMRI and DTI, as advanced MR imaging technology is readily available and automated image analysis methodology have recently been transferred from the human to animal imaging setting. For this purpose, we developed a synergistic, parallel approach to imaging and image analysis for the human and the rodent branch of our study. We propose an equivalent design in both the selection of the developmental assessment stage and the neuroimaging setup. This approach brings significant advantages to study neurobiological features of early brain development that are common to animals and humans but also preserve analysis capabilities only possible in animal research. This paper presents the main framework and individual methods for the proposed cross-species study design, as well as preliminary DTI cross-species comparative results in the intra-uterine cocaine-exposure study.

Use of High Resolution 3D Diffusion Tensor Imaging to Study Brain White Matter Development in Live Neonatal Rats.

High resolution diffusion tensor imaging (DTI) can provide important information on brain development, yet it is challenging in live neonatal rats due to the small size of neonatal brain and motion-sensitive nature of DTI. Imaging in live neonatal rats has clear advantages over fixed brain scans, as longitudinal and functional studies would be feasible to understand neuro-developmental abnormalities. In this study, we developed imaging strategies that can be used to obtain high resolution 3D DTI images in live neonatal rats at postnatal day 5 (PND5) and PND14, using only 3 h of imaging acquisition time. An optimized 3D DTI pulse sequence and appropriate animal setup to minimize physiological motion artifacts are the keys to successful high resolution 3D DTI imaging. Thus, a 3D rapid acquisition relaxation enhancement DTI sequence with twin navigator echoes was implemented to accelerate imaging acquisition time and minimize motion artifacts. It has been suggested that neonatal mammals possess a unique ability to tolerate mild-to-moderate hypothermia and hypoxia without long term impact. Thus, we additionally utilized this ability to minimize motion artifacts in magnetic resonance images by carefully suppressing the respiratory rate to around 15/min for PND5 and 30/min for PND14 using mild-to-moderate hypothermia. These imaging strategies have been successfully implemented to study how the effect of cocaine exposure in dams might affect brain development in their rat pups. Image quality resulting from this in vivo DTI study was comparable to ex vivo scans. fractional anisotropy values were also similar between the live and fixed brain scans. The capability of acquiring high quality in vivo DTI imaging offers a valuable opportunity to study many neurological disorders in brain development in an authentic living environment.

Automatic Skull-stripping of Rat MRI/DTI Scans and Atlas Building.

3D Magnetic Resonance (MR) and Diffusion Tensor Imaging (DTI) have become important noninvasive tools for the study of animal models of brain development and neuropathologies. Fully automated analysis methods adapted to rodent scale for these images will allow high-throughput studies. A fundamental first step for most quantitative analysis algorithms is skull-stripping, which refers to the segmentation of the image into two tissue categories, brain and non-brain. In this manuscript, we present a fully automatic skull-stripping algorithm in an atlas-based manner. We also demonstrate how to either modify an external atlas or to build an atlas from the population itself to present a self-contained approach. We applied our method to three datasets of rat brain scans, at different ages (PND5, PND14 and adult), different study groups (control, ethanol exposed), as well as different image acquisition parameters. We validated our method by comparing the automated skull-strip results to manual delineations performed by our expert, which showed a discrepancy of less than a single voxel on average. We thus demonstrate that our algorithm can robustly and accurately perform the skull-stripping within one voxel of the manual delineation, and in a fraction of the time it takes a human expert.

Automatic cortical thickness analysis on rodent brain.

Localized difference in the cortex is one of the most useful morphometric traits in human and animal brain studies. There are many tools and methods already developed to automatically measure and analyze cortical thickness for the human brain. However, these tools cannot be directly applied to rodent brains due to the different scales; even adult rodent brains are 50 to 100 times smaller than humans. This paper describes an algorithm for automatically measuring the cortical thickness of mouse and rat brains. The algorithm consists of three steps: segmentation, thickness measurement, and statistical analysis among experimental groups. The segmentation step provides the neocortex separation from other brain structures and thus is a preprocessing step for the thickness measurement. In the thickness measurement step, the thickness is computed by solving a Laplacian PDE and a transport equation. The Laplacian PDE first creates streamlines as an analogy of cortical columns; the transport equation computes the length of the streamlines. The result is stored as a thickness map over the neocortex surface. For the statistical analysis, it is important to sample thickness at corresponding points. This is achieved by the particle correspondence algorithm which minimizes entropy between dynamically moving sample points called particles. Since the computational cost of the correspondence algorithm may limit the number of corresponding points, we use thin-plate spline based interpolation to increase the number of corresponding sample points. As a driving application, we measured the thickness difference to assess the effects of adolescent intermittent ethanol exposure that persist into adulthood and performed t-test between the control and exposed rat groups. We found significantly differing regions in both hemispheres.

Disruption of maternal parenting circuitry by addictive process: rewiring of reward and stress systems.

Addiction represents a complex interaction between the reward and stress neural circuits, with increasing drug use reflecting a shift from positive reinforcement to negative reinforcement mechanisms in sustaining drug dependence. Preclinical studies have indicated the involvement of regions within the extended amygdala as subserving this transition, especially under stressful conditions. In the addictive situation, the reward system serves to maintain habitual behaviors that are associated with the relief of negative affect, at the cost of attenuating the salience of other rewards. Therefore, addiction reflects the dysregulation between core reward systems, including the prefrontal cortex (PFC), ventral tegmental area (VTA), and nucleus accumbens (NAc), as well as the hypothalamic-pituitary-adrenal axis and extended amygdala of the stress system. Here, we consider the consequences of changes in neural function during or following addiction on parenting, an inherently rewarding process that may be disrupted by addiction. Specifically, we outline the preclinical and human studies that support the dysregulation of reward and stress systems by addiction and the contribution of these systems to parenting. Increasing evidence suggests an important role for the hypothalamus, PFC, VTA, and NAc in parenting, with these same regions being those dysregulated in addiction. Moreover, in addicted adults, we propose that parenting cues trigger stress reactivity rather than reward salience, and this may heighten negative affect states, eliciting both addictive behaviors and the potential for child neglect and abuse.

Cocaine Exposure and Children's Self-Regulation: Indirect Association via Maternal Harshness.

OBJECTIVES: This study examined the association between prenatal cocaine exposure and children's self-regulation at 3 years of child age. In addition to direct effects of prenatal cocaine exposure on children's self-regulation, we hypothesized there would be indirect associations between cocaine exposure and self-regulation via higher maternal harshness and poor autonomic regulation in infancy. METHODS: The sample consisted of 216 mother-infant dyads recruited at delivery from local area hospitals (116 cocaine-exposed, 100 non-exposed). Infant autonomic regulation was measured at 7 months of age during an anger/frustration task, maternal harshness was coded from observations of mother-toddler interactions at 2 years of age, and children's self-regulation was measured at 3 years of age using several laboratory paradigms. RESULTS: Contrary to hypotheses, there were no direct associations between maternal cocaine use during pregnancy and children's self-regulation. However, results from testing our conceptual model including the indirect effects via maternal harshness or infant parasympathetic regulation indicated that this model fit the data well, χ(2) (23) = 34.36, p > 0.05, Comparative Fit Index = 0.95, RMSEA = 0.05. Cocaine using mothers displayed higher intensity of harshness toward their toddlers during lab interactions across a variety of tasks at 2 years of age (ß = 0.23, p < 0.05), and higher intensity of harshness at 2 years was predictive of lower self-regulation at 3 years (ß = -0.36, p < 0.01). Maternal cocaine use was also predictive of a non-adaptive increase in respiratory sinus arrhythmia (RSA) from baseline to the negative affect task, but RSA change in infancy was not predictive of self-regulation at 3 years. CONCLUSION: RESULTS are supportive of animal models indicating higher aggression among cocaine treated dams, and indicate that higher maternal harshness among cocaine using mothers is predictive of child self-regulatory outcomes in the preschool period.

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.

Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors: Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure.

Prenatal cocaine (PC) exposure negatively impacts the developing nervous system, including numerous changes in serotonergic signaling. Cocaine, a competitive antagonist of the serotonin transporter, similar to selective serotonin reuptake inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving the direct mechanism through which cocaine disrupts the developing serotonin system unclear. In order to understand the role of the serotonin transporter in cocaine's effect on the serotonergic system, we compare reports concerning PC and prenatal antidepressant exposure and conclude that PC exposure affects many facets of serotonergic signaling (serotonin levels, receptors, transporters) and that these effects differ significantly from what is observed following prenatal SSRI exposure. Alterations in serotonergic signaling are dependent on timing of exposure, test regimens, and sex. Following PC exposure, behavioral disturbances are observed in attention, emotional behavior and stress response, aggression, social behavior, communication, and like changes in serotonergic signaling, these effects depend on sex, age and developmental exposure. Vulnerability to the effects of PC exposure can be mediated by several factors, including allelic variance in serotonergic signaling genes, being male (although fewer studies have investigated female offspring), and experiencing the adverse early environments that are commonly coincident with maternal drug use. Early environmental stress results in disruptions in serotonergic signaling analogous to those observed with PC exposure and these may interact to produce greater behavioral effects observed in children of drug-abusing mothers. We conclude that based on past evidence, future studies should put a greater emphasis on including females and monitoring environmental factors when studying the impact of PC exposure.

Effects of chronic and intermittent cocaine treatment on dominance, aggression, and oxytocin levels in post-lactational rats.

RATIONALE: Little is known about mechanisms underlying female rodent aggression during the late postpartum period with no pups present. Studies of aggression, dominance, and oxytocin (OT) response in cocaine-treated females are sparse. OBJECTIVES: This study was designed to examine dominance (drinking success) and aggression in a limited-access drinking model of water competition. Acute OT level measures were made on postpartum day (PPD) 36 in several brain regions of interest. Chronic and intermittent cocaine- and saline-treated and untreated rats 10 days post-weaning were tested (without pups) over PPDs 31-35 following cessation of cocaine treatment 10-30 days before testing. METHODS: Subjects were water-deprived overnight, and triads consisting of an untreated control (UN), a chronic continuous saline-treated (CS), and chronic continuous cocaine-treated (CC; 30 mg/kg/day throughout gestation) or a UN, an intermittent saline-treated (IS), and an intermittent cocaine-treated (IC; 30 mg/kg two consecutive days every 4 days throughout gestation until PPD 20) female were tested for aggression and drinking behavior during 5 min sessions on five consecutive days. The amygdala, medial preoptic area (MPOA), and ventral tegmental area were assayed for OT levels. RESULTS: CC and IC females were more aggressive than controls, but only IC females drank more often than controls. OT levels were lower in the MPOA of IC and CC females than in controls. CONCLUSIONS: Findings demonstrate that long after cessation of treatment, CC- and IC-treated non-lactating females (no pups present) had higher rates of aggression, altered drinking behavior, and acutely lower MPOA OT levels.

Simultaneous prenatal ethanol and nicotine exposure affect ethanol consumption, ethanol preference and oxytocin receptor binding in adolescent and adult rats.

Ethanol consumption and smoking during pregnancy are common, despite the known adverse effects on the fetus. The teratogenicity of each drug independently is well established; however, the effects of concurrent exposure to ethanol and nicotine in preclinical models remain unclear. This study examined the impact of simultaneous prenatal exposure to both ethanol and nicotine on offspring ethanol preference behaviors and oxytocin system dynamics. Rat dams were given liquid diet (17% ethanol derived calories (EDC)) on gestational day (GD) 5 and 35% EDC from GD 6-20 and concurrently an osmotic minipump delivered nicotine (3-6mg/kg/day) from GD 4-postpartum day 10. Offspring were tested for ethanol preference during adolescence (postnatal day (PND) 30-43) and again at adulthood (PND 60-73), followed by assays for oxytocin mRNA expression and receptor binding in relevant brain regions. Prenatal exposure decreased ethanol preference in males during adolescence, and decreased consumption and preference in females during adulthood compared to controls. Oxytocin receptor binding in the nucleus accumbens and hippocampus was increased in adult prenatally exposed males only. Prenatal exposure to these drugs sex-specifically decreased ethanol preference behavior in offspring unlike reports for either drug separately. The possible role of oxytocin in reduction of ethanol consumption behavior is highlighted.

Cocaine disrupts pup-induced maternal behavior in juvenile and adult rats.

Impaired onset of maternal behavior in first generation rat dams was previously correlated with rearing by cocaine-treated dams and prenatal cocaine exposure. Pup-induced maternal behavior in non-lactating rats has not been examined with regard to cocaine exposure and rearing conditions. First generation male and female juveniles and young adult males reared by cocaine-treated or control dams and prenatally exposed to either cocaine or control conditions were tested for pup-induced maternal behavior at postnatal days 28 and 60. We now report disruptions in pup-induced maternal behavior in both 28 and 60 day old first generation offspring attributable to rearing condition and prenatal cocaine exposure.