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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

Cocaine treatment and prenatal environment interact to disrupt intergenerational maternal behavior in rats.

The link between impaired maternal behavior (MB) and cocaine treatment could result from drug-induced 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.

Deficits in plasma oxytocin responses and increased negative affect, stress, and blood pressure in mothers with cocaine exposure during pregnancy.

In animals, oxytocin enhances maternal behavior and lowers blood pressure (BP) and negative affect, while parturitional cocaine disrupts oxytocin activity and increases maternal neglect and aggression. Thus, we compared oxytocin, BP, maternal behavior, and affect in mothers of infants who used cocaine (cocaine, n = 10) or did not (no drug, n = 25) during pregnancy. Laboratory BP and circulating oxytocin, catecholamines, and cortisol were examined before and during a speech stressor on 2 days, with vs.

Gestational treatment with cocaine and fluoxetine alters oxytocin receptor number and binding affinity in lactating rat dams.

Cocaine administered chronically throughout gestation has been correlated with deficits in maternal behavior, increased maternal aggressive behavior and decreased oxytocin levels in rats. In addition to its effects on oxytocin levels, cocaine is a potent serotonergic, dopaminergic and noradrenergic reuptake inhibitor. Alterations in the dopaminergic and serotonergic systems have been suggested as possibly having a role in cocaine-induced maternal aggression.

An oxytocin antagonist infused into the central nucleus of the amygdala increases maternal aggressive behavior.

Decreased oxytocin levels in the amygdalas of rat dams following chronic gestational cocaine exposure have been correlated with heightened maternal aggressive behavior. In this experiment, drug-naive dams were implanted with bilateral cannulas into the central nucleus of the amygdala (CNA) or control area and infused with 1,000 or 500 ng of an oxytocin antagonist (OTA) or buffer, 4 hr before testing. Behavior was compared among dams infused with OTA into target areas just outside the CNA and cocaine-treated dams (infused with buffer).

Developmental effects of prenatal cocaine exposure on 5-HT1A receptors in male and female rat offspring.

Prenatal cocaine exposure results in behavioral abnormalities throughout development in rats, but little is known regarding the biological mechanisms underlying these abnormalities. Pregnant rats received subcutaneous twice-daily injections (1 ml/kg) of normal saline or 15 mg/kg of cocaine hydrochloride throughout gestation (gestation days 1-20). Following delivery, pups were placed with untreated surrogates.

Presynaptic dopaminergic function is largely unaltered in mesolimbic and mesostriatal terminals of adult rats that were prenatally exposed to cocaine.

Fast-scan cyclic voltammetry in brain slices and postmortem tissue content assessment were used to evaluate presynaptic dopaminergic function in the caudate putamen and nucleus accumbens of adult male rats (180+ days old) that were prenatally treated with either cocaine or saline. Experiments were carried out to test whether there were differences in dopamine release, reuptake, autoreceptor function or the tissue levels of dopamine and its metabolites between cocaine- and saline-exposed rats. We report that presynaptic dopaminergic function remains largely intact in adult rats that were prenatally exposed to cocaine.