Moderate adolescent chronic intermittent ethanol exposure sex-dependently disrupts synaptic transmission and kappa opioid receptor function in the basolateral amygdala of adult rats

Przybysz, Kathryn R.; Gamble, Meredith E.

doi:10.1016/j.neuropharm.2021.108512

Cited by 8 publications

(8 citation statements)

References 65 publications

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“…Alternatively, AIE exposure in females, in the absence of PNN expression differences, led to reduced vGlut2 synaptic puncta, potentially disrupting the shift in excitatory/inhibitory balance occurring during adolescence (Caballero et al, 2021). Previously reported female-specific effects of adolescent ethanol include increased glutamate transmission in the basolateral amygdala (Przybysz et al, 2021) and altered metabotropic glutamate receptor function (Kasten et al, 2020). It is important to consider that our finding with vGlut2 puncta were distinctly expressed on PNNs and may not represent a general change in vGlut2 expression across the PrL.…”

Section: Discussionmentioning

confidence: 99%

Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure

Towner,

Coleman,

Goyden

et al. 2024

Preprint

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Adolescent intermittent ethanol (AIE) exposure in rats leads to social deficits. Parvalbumin (PV) expressing interneurons in the prelimbic cortex (PrL) contribute to social behavior, and perineuronal nets (PNNs) within the PrL preferentially encompass PV interneurons, acting as significant regulators of these cells. AIE exposure increases PNNs, however, it is unknown if this upregulation contributes to AIE-induced social impairments. The current study was designed to determine the effect of AIE exposure on PNN expression in the PrL and to assess whether PNN dysregulation contributes to social deficits elicited by AIE. cFos-LacZ male and female rats were exposed every other day to tap water or ethanol (4g/kg, 25% w/v) via intragastric gavage between postnatal day (P) 25-45. We evaluated neuronal activation by β-galactosidase expression and PNN levels either at the end of the exposure regimen on P45 and/or in adulthood on P70. In addition, we used Chondroitinase ABC (ChABC) to deplete PNNs following adolescent exposure (P48) and allowed for PNN restoration before social testing in adulthhod. AIE exposure increased PNN expressionin the PrL of adult males, whereas a decrease in PNNs was evident immediately following AIE. Vesicular glutamate transporter 2 (vGlut2) and vesicular GABA transporter (vGat) near PNNs were moderately downregulated only in AIE-exposed females. Gene expression of PNN components were largely unaffected by AIE exposure. Removal and reestablishment of PNNs in the PrL led to upregulation of PNNs and social impairments in males, regardless of adolescent exposure. These data suggest that AIE exposure in males produces an upregulation of PrL PNNs that likely contribute to social impairments induced by AIE.

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Section: Discussionmentioning

confidence: 99%

Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure

Towner,

Coleman,

Goyden

et al. 2024

Preprint

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“…Interestingly, the fact that norBNI did not increase CeA GABA release after Pentylone and MDMA self-administration may suggest a loss of tonic dynorphin signaling in the CeA at first sight, but it could also stem from alternative or non-canonical KOR signaling cascades resulting from repeated drug exposure ( Nguyen et al, 2017b , 2021 ). Indeed, KOR signaling has been shown to be highly sensitive to stressful events ( Polter et al, 2017 ; Estave et al, 2020 ; Przybysz et al, 2021 ) and recent studies show constitutive activity of KOR at GABAergic synapses in the ventral tegmental area in response to brief cold-water swim stress leading to altered effects of KOR antagonism ( Polter et al, 2017 ). Moreover, KOR activation is coupled to several distinct intracellular signaling cascades involving G-protein coupled Receptor Kinases (GRK) and members of the mitogen-activated protein kinase (MAPK) family or β-arrestin-dependent pathways, amongst other classical G-protein mediated mechanisms ( Bruchas and Chavkin, 2010 ; Lovell et al, 2015 ; Ho et al, 2018 ; Uprety et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Self-Administration of Entactogen Psychostimulants Dysregulates Gamma-Aminobutyric Acid (GABA) and Kappa Opioid Receptor Signaling in the Central Nucleus of the Amygdala of Female Wistar Rats

Khom

Nguyen

Vandewater

et al. 2021

Front. Behav. Neurosci.

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Male rats escalate intravenous self-administration of entactogen psychostimulants, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxymethamphetamine (MDMA) under extended access conditions, as with typical psychostimulants. Here, we investigated whether female rats escalate self-administration of methylone, 3,4-methylenedioxypentedrone (pentylone), and MDMA and then studied consequences of MDMA and pentylone self-administration on GABAA receptor and kappa opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA), a brain area critically dysregulated by extended access self-administration of alcohol or cocaine. Adult female Wistar rats were trained to self-administer methylone, pentylone, MDMA (0.5 mg/kg/infusion), or saline-vehicle using a fixed-ratio 1 response contingency in 6-h sessions (long-access: LgA) followed by progressive ratio (PR) dose-response testing. The effects of pentylone-LgA, MDMA-LgA and saline on basal GABAergic transmission (miniature post-synaptic inhibitory currents, mIPSCs) and the modulatory role of KOR at CeA GABAergic synapses were determined in acute brain slices using whole-cell patch-clamp. Methylone-LgA and pentylone-LgA rats similarly escalated their drug intake (both obtained more infusions compared to MDMA-LgA rats), however, pentylone-LgA rats reached higher breakpoints in PR tests. At the cellular level, baseline CeA GABA transmission was markedly elevated in pentylone-LgA and MDMA-LgA rats compared to saline-vehicle. Specifically, pentylone-LgA was associated with increased CeA mIPSC frequency (GABA release) and amplitude (post-synaptic GABAA receptor function), while mIPSC amplitudes (but not frequency) was larger in MDMA-LgA rats compared to saline rats. In addition, pentylone-LgA and MDMA-LgA profoundly disrupted CeA KOR signaling such as both KOR agonism (1 mM U50488) and KOR antagonism (200 nM nor-binaltorphimine) decreased mIPSC frequency suggesting recruitment of non-canonical KOR signaling pathways. This study confirms escalated self-administration of entactogen psychostimulants under LgA conditions in female rats which is accompanied by increased CeA GABAergic inhibition and altered KOR signaling. Collectively, our study suggests that CeA GABA and KOR mechanisms play a critical role in entactogen self-administration like those observed with escalation of alcohol or cocaine self-administration.

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“…A growing body of evidence indicates sex-differences in these functions ( Cahill et al., 2004 ; Canli et al., 2002 ; Greiner et al., 2019 ; Gruene et al., 2015 ; Lebron-Milad and Milad, 2012 ). Moreover, the BLA is implicated in the etiology of neuropsychiatric diseases including post-traumatic stress disorder, depression, and anxiety ( Daviu et al., 2019 ; Mahan and Ressler, 2012 ; Nestler et al., 2002 ), characterized by their higher prevalence in the female population ( Christiansen and Berke, 2020 ; Kuehner, 2017 ; McLean et al., 2011 ).While the study of females’ brains and sex differences in preclinical research have recently gained momentum ( Shansky and Murphy, 2021 ), sex differences in the functions of the BLA have mostly been studied in pathological rodent models ( Blume et al., 2019 ; Geary et al., 2021 ; Guadagno et al., 2020 ; Przybysz et al., 2021 ) and the physiological development of the female BLA remains partially understood.…”

Section: Introductionmentioning

confidence: 99%

Sex-specific divergent maturational trajectories in the postnatal rat basolateral amygdala

et al. 2022

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Moderate adolescent chronic intermittent ethanol exposure sex-dependently disrupts synaptic transmission and kappa opioid receptor function in the basolateral amygdala of adult rats

Cited by 8 publications

References 65 publications

Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure

Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure

Self-Administration of Entactogen Psychostimulants Dysregulates Gamma-Aminobutyric Acid (GABA) and Kappa Opioid Receptor Signaling in the Central Nucleus of the Amygdala of Female Wistar Rats

Sex-specific divergent maturational trajectories in the postnatal rat basolateral amygdala

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