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

Department of Psychiatry, University of North Carolina, 430 Taylor Hall, CB# 7096, Chapel Hill, NC 27599, USA.
Psychopharmacology (Impact Factor: 3.88). 08/2010; 211(2):175-85. DOI: 10.1007/s00213-010-1877-9
Source: PubMed


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.
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.
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.
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.
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.

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Available from: Josephine M Johns, Jul 04, 2015
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    • "Extensive evidence also outlines the detrimental effects of chronic administration of the psychostimulant cocaine on normative OTergic functioning and associated social behaviors in both animals and humans (Johns et al., 2010; Light et al., 2004). "
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    Experimental and Clinical Psychopharmacology 10/2012; 20(6). DOI:10.1037/a0029976 · 2.71 Impact Factor
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    • "One potential mechanism for the effects of cocaine on maternal aggression is through the modulation of central oxytocin (OXT). Cocaine induced changes in central OXT may mediate the increase in aggression, as maternal aggression has been associated with decreased oxytocin activity in the amygdala [47, 52] and mPOA [67]. Gestational cocaine treatment elevates maternal aggression on day 6 and results in decreased OXT, increased OXT receptor binding density, and decreased OXT receptor affinity in the amygdala, [68]. "
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    ABSTRACT: Drug addiction is a chronic relapsing disorder that involves drug seeking and abuse despite the negative social and health consequences. While the potential effects of cocaine on child development have been extensively studied over the last 30 years, few researchers have focused on the effects of cocaine on maternal behavior, which includes offspring care and maternal aggression towards an unfamiliar individual. In humans, maternal cocaine use can lead to child neglect, abuse, and disrupt the mother-child bond. While it has been argued the developmental effects of maternal cocaine use on children were initially overstated, it is clear that disruptions of typical maternal behavior (i.e. postpartum depression, anxiety disorders) are detrimental to the physical and emotional health of offspring. Cocaine use in mothers is commonly associated with psychological disorders, including depression and anxiety, and it is postulated that many of the negative effects of maternal cocaine use on offspring are mediated through changes in maternal behavior. This review will summarize research on cocaine and maternal behavior in animal and human studies, discuss potential mechanisms, and suggest therapeutic strategies for treating cocaine-affected maternal behavior which may improve the physical and behavioral health of both mother and child. The primary objective is to stimulate future communication, cooperation, and collaboration between researchers who use animals and humans to study cocaine and maternal behavior.
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    • "In the MeA, cocaine induced an increase in dendritic spine density in the rat dams. Gestational cocaine has previously been shown to increase dopamine and DOPAC levels (Lubin et al., 2003), decrease oxytocin levels (Johns et al., 2010) and result in an up-regulation of oxytocin receptors in the amygdala of rats six days after birth (Johns et al., 2004). In contrast, in the present study cocaine exposure resulted in a decrease in dendritic spine density in the MPOA of dams. "
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    ABSTRACT: Cocaine use during pregnancy induces profound neural and behavioral deficits in both mother and offspring. The present study was designed to compare the effects of cocaine exposure on spine density of postpartum and virgin female rat brains. Timed, pregnant, primiparous rats were injected with either cocaine (30 mg/kg) or saline, once daily, from gestational day 8 to 20. Twenty-four hours after giving birth, dam brains were processed for Golgi-impregnation. Virgin females were also injected with the same dose of cocaine or saline for 12 days and sacrificed 24 h after the last injection for comparison. Pregnant rats had significantly greater spine density in the medial amygdala (MeA) and medial preoptic area (MPOA) and lower spine density in CA1 than virgin females independent of cocaine treatment. Cocaine significantly increased dendritic spine density on the apical branch of pyramidal cells in the prefrontal cortex (PFC, 15%), both apical (13%) and basal (14.8%) branches of CA1 and cells in the MeA (28%) of pregnant rats. In the MPOA, cocaine administration resulted in a decrease in dendritic spine density (14%) in pregnant rats. In virgin females, cocaine had fewer effects but did increase dendritic spine density on both branches of CA1 neurons and in the MeA. The present study is the first to demonstrate that spine density differs between pregnant and virgin females and that pregnancy makes the brain more vulnerable to cocaine, which has important clinical implications.
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