scholarly journals Early Life Stress Promotes Heroin Seeking But Does Not Alter the Excitability of Insular Pyramidal Cells Targeting the Nucleus Accumbens

2021 ◽  
Vol 15 ◽  
Author(s):  
Jonna M. Leyrer-Jackson ◽  
Paula F. Overby ◽  
Erin K. Nagy ◽  
M. Foster Olive
Keyword(s):  
Nucleus Accumbens ◽  
Adverse Childhood Experiences ◽  
Life Stress ◽  
Early Life ◽  
Pyramidal Neurons ◽  
Early Life Stress ◽  
Self Administration ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Seeking Behavior

A number of retrospective studies have demonstrated adverse childhood experiences are associated with increased vulnerability to substance use disorders, including opioid use disorders (OUDs). These adverse childhood experiences, also referred to as early life stress (ELS), can be modeled in laboratory animals by various paradigms including limited bedding and nesting (LBN) procedures. Studies using rodent models of ELS have been shown to recapitulate various aspects of OUDs, including relapse propensity and perseverance of drug-seeking behavior. In the current study, we utilized the LBN paradigm to explore potential effects on heroin self-administration, extinction, and relapse-like behaviors in male and female rats. We also utilized in vitro whole-cell electrophysiology to examine the effects of LBN and repeated heroin administration on the excitability of pyramidal neurons in the anterior insular cortex (AIC) projecting to the nucleus accumbens core (NAc), as recent studies suggest that this circuit may mediate various aspects of OUDs and may be compromised as a result of either ELS or OUDs. We observed that compared to control animals, rats exposed to LBN conditions during postnatal days 2–9 showed increased breakpoints for heroin self-administration under a progressive ratio schedule of reinforcement, impaired extinction of heroin-seeking behavior, and increased reinstatement of heroin-seeking behavior induced by heroin-associated cues. No effect of LBN rearing conditions were observed on the acquisition and maintenance of heroin self-administration, and no sex differences in heroin intake were observed. LBN and control reared animals showed no differences in the excitability of AIC-NAc pyramidal neurons, but animals treated with repeated heroin showed decreased excitability of these neurons through a significant increase in rheobase and reduction in action potentials induced by depolarizing currents. Together, these results suggest that ELS exposure produces exacerbations of heroin seeking behavior without parallel effects on AIC-NAc excitability, although heroin itself reduces the excitability of these neurons.

scholarly journals Interactions between Early Life Stress, Nucleus Accumbens MeCP2 Expression, and Methamphetamine Self-Administration in Male Rats

2016 ◽  
Vol 41 (12) ◽  
pp. 2851-2861 ◽  
Author(s):  
Candace R Lewis ◽  
Ryan M Bastle ◽  
Tawny B Manning ◽  
Sarah M Himes ◽  
Paulette Fennig ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Male Rats ◽  
Self Administration

scholarly journals Early-life stress alters sleep structure and the excitatory-inhibitory balance in the nucleus accumbens in aged mice

2019 ◽  
Vol 132 (13) ◽  
pp. 1582-1590
Author(s):  
Ting Wang ◽  
Hong-Li Wang ◽  
Rui Liu ◽  
Han Wang ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Sleep Structure ◽  
Aged Mice

scholarly journals Early Life Stress Associated With Increased Striatal N-Acetyl-Aspartate: Cerebrospinal Fluid Corticotropin-Releasing Factor Concentrations, Hippocampal Volume, Body Mass, and Behavioral Correlates

2018 ◽  
Vol 2 ◽  
pp. 247054701876845 ◽  
Author(s):  
Jeremy D. Coplan ◽  
Dunyue Lu ◽  
Alexander M. El Sehamy ◽  
Cheuk Tang ◽  
Andrea P. Jackowski ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Nucleus Accumbens ◽  
Body Mass ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Hippocampal Volume ◽  
Corticotropin Releasing Factor ◽  
Resonance Spectroscopy ◽  
Stress Markers

Introduction Using proton magnetic resonance spectroscopy imaging, the effects of early life stress on nonhuman primate striatal neuronal integrity were examined as reflected by N-acetyl aspartate (NAA) concentrations. NAA measures were interrogated through examining their relationship to previously documented early life stress markers—cerebrospinal fluid corticotropin-releasing factor concentrations, hippocampal volume, body mass, and behavioral timidity. Rodent models of depression exhibit increases in neurotrophic effects in the nucleus accumbens. We hypothesized that rearing under conditions of early life stress (variable foraging demand, VFD) would produce persistent elevations of NAA concentrations (in absolute or ratio form) in ventral striatum/caudate nucleus (VS/CN) with altered correlation to early life stress markers. Methods Eleven bonnet macaque males reared under VFD conditions and seven age-matched control subjects underwent proton magnetic resonance spectroscopy imaging during young adulthood. Voxels were placed over VS/CN to capture nucleus accumbens. Cisternal cerebrospinal fluid corticotropin-releasing factor concentrations, hippocampal volume, body mass, and response to a human intruder had been previously determined. Results VFD-reared monkeys exhibited significantly increased NAA/creatine concentrations in right VS/CN in comparison to normally reared controls, controlling for multiple comparisons. In comparison to controls, VFD cerebrospinal fluid corticotropin-releasing factor concentrations were directly associated with right VS/CN absolute NAA. Left hippocampal volume was inversely associated with left VS/CN NAA/creatine in VFD reared but not in controls. Disruption of a normative inverse correlation between left VS/CN NAA and body mass was noted in VFD. Only non-VFD subjects exhibited a direct relationship between timidity response to an intruder and right VS/CN NAA. Conclusion Early life stress produced persistent increases in VS/CN NAA, which demonstrated specific patterns of association (or lack thereof) to early life stress markers in comparison to non-VFD subjects. The data are broadly consistent with a stable nonhuman primate phenotype of anxiety and mood disorder vulnerability whereby in vivo indicators of neuronal integrity, although reduced in hippocampus, are increased in striatum. The findings may provide a catalyst for further studies in humans and other species regarding a reciprocal hippocampal/nucleus accumbens relationship in affective disorders.

scholarly journals Potentiation of glutamatergic synaptic transmission onto lateral habenula neurons following early life stress and intravenous morphine self-administration in rats

2020 ◽  
Author(s):  
Ludovic D. Langlois ◽  
Rina Y. Berman ◽  
Ryan D. Shepard ◽  
Sarah C. Simmons ◽  
Mumeko C. Tsuda ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Sucrose Preference ◽  
Male Rats ◽  
Self Administration ◽  
Lateral Habenula ◽  
Glutamatergic Synaptic Transmission ◽  
Intravenous Morphine

AbstractEarly life stress (ELS) presents an important risk factor for drug addiction and comorbid depression and anxiety through persistent effects on the mesolimbic dopamine (DA) pathways1. Using an ELS model for child neglect (a single 24 h episode of maternal deprivation, MD) in rats, recent published works from our lab show that MD induces dysfunction in ventral tegmental area (VTA) DA neurons 2–4 and its negative controller, the lateral habenula (LHb) 5–7. In regard to LHb, MD-induced potentiation of glutamatergic synaptic transmission onto LHb neurons shifts the coordination of excitation/inhibition (E/I) balance towards excitation, resulting in an increase in the overall spontaneous neuronal activity with elevation in bursting and tonic firing, and intrinsic excitability of LHb neurons in early adolescent male rats 5–7. Here, we explored how MD affects intravenous morphine self-administration (MSA) acquisition and sucrose preference as well as glutamatergic synaptic function in LHb neurons of adult male rats self-administering morphine. We found that MD-induced increases in LHb neuronal and glutamatergic synaptic activity and E/I ratio persisted into adulthood. Moreover, MD significantly reduced morphine intake, triggered anhedonia-like behavior in the sucrose preference test (SPT), and was associated with persistent glutamatergic potentiation 24h after the last MSA session. MSA also triggered postsynaptic glutamatergic potentiation in LHb neurons of control rats during this time period. Our data highlights that ELS-induced glutamatergic plasticity in LHb may dampen the positive reinforcing properties of natural rewards and opioids, and contribute to the development of anhedonic and dysphoric states associated with opioids.

scholarly journals Adolescent Stress Increases Adult Ethanol Self-administration and Alters Ventral Tegmental Area GABA Signaling

2019 ◽  
Author(s):  
David A Connor ◽  
Ruthie E Wittenberg ◽  
Jillian Drogin ◽  
Allison Mak ◽  
John A Dani
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Alcohol Use Disorders ◽  
Early Life Stress ◽  
Male Rats ◽  
Stress Exposure ◽  
Self Administration ◽  
Adolescent Stress ◽  
Gaba Signaling

AbstractAlcohol use disorders (AUDs) continue to be a significant public health problem. Early life stress and adversity have long-lasting effects on a wide range of behaviors, including responses to drugs of abuse. Epidemiological evidence indicates that exposure to early life stress contributes to alcohol use disorders and, while it is known that stress and alcohol both act on overlapping mesolimbic circuitry, the cellular mechanisms underlying the relationship between stress and alcohol intake are not well understood. Previous work has demonstrated that acute stress increases ethanol intake mediated by changes in GABA signaling within the ventral tegmental area (VTA). Here we investigated if adolescent stress exposure might elicit long-term, persistent increases in ethanol self-administration associated with altered VTA GABA signaling. To this end, we exposed adolescent postnatal day (PND) 28 male rats to 14 days of chronic variable stress (CVS) and then examined operant ethanol self-administration begun at least 30 days later. We found that adolescent stress exposure resulted in significantly increased ethanol self-administration in adulthood. In contrast, adult (PND 82) male rats exposed to the same CVS protocol did not display increased ethanol self-administration that was begun 30 days later. Furthermore, we found that adolescent stress exposure resulted in enhancement of ethanol-induced GABA signaling onto VTA dopamine neurons and impairments in VTA GABA chloride homeostasis. The results indicate that adolescence is a period vulnerable to stress, which produces long-term changes in VTA GABA signaling associated with increased ethanol self-administration behavior.

scholarly journals Adverse childhood experiences and early life inflammation in the Avon longitudinal study of parents and children

2020 ◽  
Vol 122 ◽  
pp. 104914
Author(s):  
Rebecca E Lacey ◽  
Mel Bartley ◽  
Michelle Kelly-Irving ◽  
Leonardo Bevilacqua ◽  
Eleonora Iob ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Adverse Childhood Experiences ◽  
Early Life ◽  
Childhood Experiences ◽  
Parents And Children ◽  
Adverse Childhood ◽  
Avon Longitudinal Study
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