Effects of early life stress on cocaine conditioning and AMPA receptor composition are sex-specific and driven by TNF

Ganguly, Prabarna; Rowe, June R.; Demaestri, Camila; Brenhouse, Heather C.

doi:10.1016/j.bbi.2019.01.006

Cited by 57 publications

(49 citation statements)

References 60 publications

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“…Therefore, our results support early life adversity as a critical non-genetic risk factor for the development of drug-related problems during adolescence. These findings add relevant data to the, so far, scarce literature suggesting that MS causes alterations that influence vulnerability to drug abuse in adolescent rodents [19][20][21] . In previous studies, also using CPP, Ganguly and colleagues 19 (MS for 4 h daily, PND 2-20) and Viola and colleagues 21 (MS for 3 h daily, PND 2-15) showed that MS in adolescent male rodents, but not in female, lead to a preference for the drug paired compartment.…”

Section: Discussionsupporting

confidence: 67%

“…These findings add relevant data to the, so far, scarce literature suggesting that MS causes alterations that influence vulnerability to drug abuse in adolescent rodents [19][20][21] . In previous studies, also using CPP, Ganguly and colleagues 19 (MS for 4 h daily, PND 2-20) and Viola and colleagues 21 (MS for 3 h daily, PND 2-15) showed that MS in adolescent male rodents, but not in female, lead to a preference for the drug paired compartment. Other authors, using the maternal deprivation paradigm (MS for 24 h, PND12/13) showed increased anxiety in adolescents, but with impaired motivation for cocaine 20 .…”

Section: Discussionsupporting

confidence: 67%

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Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerability

Alves

Oliveira

Lopes

et al. 2020

Sci Rep

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The development of substance abuse problems occurs due to a diverse combination of risk factors. Among these risks, studies have reported depression and early-life stress as of importance. These two factors often occur simultaneously, however, there is a lack of understanding of how their combined effect may impact vulnerability to drug abuse in adolescence. The present study used rats with different vulnerability to depression (Wistar and Wistar-Kyoto) to investigate the impact of maternal separation (MS) on emotional state and drug addiction vulnerability during the adolescence period. Mothers and their litters were subjected to MS (180 min/day) from postnatal day 2 to 14. The offspring emotional state was assessed by observing their exploratory behavior. Drug abuse vulnerability was assessed through conditioning to cocaine. MS impacted the emotional state in both strains. Wistar responded with increased exploration, while Wistar-Kyoto increased anxiety-like behaviours. Despite the different coping strategies displayed by the two strains when challenged with the behavioural tests, drug conditioning was equally impacted by MS in both strains. Early-life stress appears to affect drug abuse vulnerability in adolescence independently of a depression background, suggesting emotional state as the main driving risk factor. The development of substance abuse problems occurs due to an almost unpredictable combination of risk factors. Among the common risk factors, mental disorder and emotional stress are constantly cited as important 1,2. Among the main mental disorders, depression is one of the most common in adolescents, inspiring great concern due to its acute and long-lasting consequences 3. Depression in adolescence affects the physical, emotional and social development and can persist and recur into adulthood 4,5. Addiction and depression can be described as having a bidirectional relationship, in which individuals that use drugs for recreational purposes are more likely to develop depression, while individuals that suffer from depression are more likely to develop addiction due to the consumption of drugs (or alcohol) to cope with the depressive symptoms 6,7. Of note, depression and drug abuse comorbidity is highly prevalent in adolescence 8. Similarly to depression, emotional stress and its impact on one's physical and affective condition may lead to the development of addiction. Furthermore, it is known that early life stress, such as children carelessness and mistreatment, can also induce anxiety and depression in adulthood 9. This issue becomes especially relevant given the likelihood of the co-occurrence of these risk factors during early life. There is increased awareness about

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Section: Discussionsupporting

confidence: 67%

Section: Discussionsupporting

confidence: 67%

Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerability

Alves

Oliveira

Lopes

et al. 2020

Sci Rep

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“…However, we did not observe significant 413 differences in GluA1 or GluA2 protein level in MSEW exposed mice. Our results are in 414 accordance with Ganguly et al (2019) who reported that males maternally separated 415 showed decreased in mPFC-Gria2 expression compared to control males. Likewise, they 416 observed that females in general, showed higher GluA2 protein level than male mice, 417 similar to our findings.…”

supporting

confidence: 89%

Cocaine-Induced Impulsivity is Differentially Expressed in Male and Female Mice Exposed to Maternal Separation and is Associated with Alterations in AMPA Receptors Subunits

Castro‐Zavala

Martín‐Sánchez

Montalvo-Martínez

et al. 2020

Preprint

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Impulsivity is a key trait in the diagnosis of major depressive disorder (MDD) and substance use disorder (SUD). MDD is a chronic illness characterized by sadness, insomnia, and loss of interest. SUD is a chronic and relapsing disorder characterized by the consumption of drugs despite their negative consequences. Among drugs of abuse, cocaine is the most consumed psychostimulant. Animal studies demonstrated that increased impulsivity predicts predisposition to acquire cocaine self-administration (SA) behaviour with an increased cocaine-intake. Moreover, early-life stress represents a vulnerability factor to develop depressive disorders and drug addiction. Maternal separation with early weaning (MSEW) is an animal model that allows examining the impact of early-life stress on cocaine abuse. In this study, we aimed to explore changes in MSEW-induced impulsivity to determine potential associations between depression-like and cocaine-seeking behaviours in male and female mice. We also evaluated possible alterations in the AMPA receptors (AMPArs) composition and glutamatergic neurotransmission. We exposed mice to MSEW and the behavioural tests were performed during adulthood. Moreover, GluA1, GluA2 mRNA and protein expression were evaluated in the medial Prefrontal Cortex (mPFC). Results showed higher impulsive cocaine-seeking in females, independently the MSEW, as well as an increase in GluA1 and GluA2 protein expression. Moreover, MSEW induced downregulation of Gria2 and increased the GluA1/GluA2 ratio, only in male mice. In conclusion, female mice expressed higher mPFC glutamatergic function, which potentiated their impulsivity during cocaine SA. Also, data indicated that MSEW alters glutamatergic function in mPFC of male mice, increasing the glutamatergic excitability.

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“…In addition, we have previously shown the importance of the dorsal hippocampus (Fakira et al, 2016;Williams et al, 2019) and AMPAR signaling in the modulation of opioid-associated contextual memory (Morón et al, 2007;Billa et al, 2009;Billa et al, 2010;Xia et al, 2011). Sex differences in AMPAR activity have also been linked to cocaine-associated memory (Bechard et al, 2018;Ganguly et al, 2019). Therefore, the novel component of sex differences in spatial memory identified here suggest that CNIH3 could play a role in sex-dependent drug-associated memory.…”

Section: Discussionmentioning

confidence: 56%

Cornichon Homolog-3 (CNIH3) Modulates Spatial Memory in Female Mice

Frye

Williams

Trousdale

et al. 2019

Preprint

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Cornichon homolog-3 (CNIH3) is an AMPA receptor (AMPAR) auxiliary protein that traffics AMPARs to the postsynaptic membrane and potentiates AMPAR signaling. AMPARs are key components of hippocampal synaptic plasticity and memory formation, however the role of CNIH3 in memory has yet to be elucidated. To study the role of CNIH3 on mouse behavior, we bred and characterized a line of Cnih3 -/mice from C57BL/6 Cnih3 tm1a(KOMP)Wtsi mice obtained from the Knockout Mouse Project (KOMP). In agreement with previous studies of CNIH3 in the brain, we observed concentrated expression of Cnih3 in the dorsal hippocampus, a region associated with spatial learning and memory. Therefore, we tested Cnih3 +/+ , Cnih3 +/-, and Cnih3 -/mice in the Barnes maze paradigm to measure spatial memory. We observed no change in spatial memory in male Cnih3 +/and Cnih3 -/mice compared to male Cnih3 +/+ controls, however, Cnih3 -/female mice made significantly more primary errors, had a higher primary latency, and took less efficient routes to the target in the maze compared to Cnih3 +/+ female mice. Next, to investigate an enhancement of spatial memory by Cnih3 overexpression, specifically in the dorsal hippocampus, we developed an AAV5 viral construct to express wild-type Cnih3 in excitatory neurons. Female mice overexpressing Cnih3 made significantly fewer errors, had a lower primary latency to the target, and took more efficient routes to the maze target compared to YFP expressing control females. No change in spatial memory was observed in male Cnih3 overexpression mice. This study, the first to identify sex-specific effects of the AMPAR auxiliary protein CNIH3 on spatial memory, provides the groundwork for future studies investigating the role of CNIH3 on sexually dimorphic AMPAR-dependent behavior and hippocampal synaptic plasticity.

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Effects of early life stress on cocaine conditioning and AMPA receptor composition are sex-specific and driven by TNF

Cited by 57 publications

References 60 publications

Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerability

Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerability

Cocaine-Induced Impulsivity is Differentially Expressed in Male and Female Mice Exposed to Maternal Separation and is Associated with Alterations in AMPA Receptors Subunits

Cornichon Homolog-3 (CNIH3) Modulates Spatial Memory in Female Mice

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