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, Sophia; Nguyen, Jacques D.; Vandewater, Sophia A.; Grant, Yanabel; Roberto, Marisa; Taffe, Michael A.

doi:10.3389/fnbeh.2021.780500

Cited by 6 publications

(3 citation statements)

References 67 publications

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“…Additional studies are needed to identify MOR-sensitive GABAergic inputs in the CeA. Like MORs, KOR activation inhibits GABA release in CeA in rats ( Przybysz et al, 2017 ) and KORs may also tonically inhibit GABA release ( Gilpin et al, 2014 ; Bloodgood et al, 2021 ; Khom et al, 2021 ). Similarly, DORs also inhibit GABA release in the CeA, but there is evidence for species differences.…”

Section: Amygdalamentioning

confidence: 99%

Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain

Reeves

Shah

Muñoz

et al. 2022

Front. Mol. Neurosci.

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Opioids mediate their effects via opioid receptors: mu, delta, and kappa. At the neuronal level, opioid receptors are generally inhibitory, presynaptically reducing neurotransmitter release and postsynaptically hyperpolarizing neurons. However, opioid receptor-mediated regulation of neuronal function and synaptic transmission is not uniform in expression pattern and mechanism across the brain. The localization of receptors within specific cell types and neurocircuits determine the effects that endogenous and exogenous opioids have on brain function. In this review we will explore the similarities and differences in opioid receptor-mediated regulation of neurotransmission across different brain regions. We discuss how future studies can consider potential cell-type, regional, and neural pathway-specific effects of opioid receptors in order to better understand how opioid receptors modulate brain function.

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Section: Amygdalamentioning

confidence: 99%

Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain

Reeves

Shah

Muñoz

et al. 2022

Front. Mol. Neurosci.

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“…Although work with conditioned place preference (CPP) has been reported with a number of synthetic cathinones (see Cheong et al, 2017; Gannon et al, 2017; Gatch et al, 2015; King, Wakeford, et al, 2015; King, Wetzell, et al, 2015; Marusich et al, 2016; Nelson et al, 2017; Risca et al, 2020), such work has not been assessed with eutylone. However, work with methylone (Karlsson et al, 2014; Miyazawa et al, 2011) has shown its ability to support place preference conditioning and eutylone’s structural isomers induce locomotor activation (Glatfelter et al, 2021; Javadi-Paydar et al, 2018; López-Arnau et al, 2012; Saha et al, 2019), substitute for cocaine and amphetamine (among other drugs of abuse) in drug discrimination assessments (Dolan et al, 2018; Gatch et al, 2019), and support intravenous self-administration (IVSA; Dolan et al, 2018; Javadi-Paydar et al, 2018; Khom et al, 2021; Lai et al, 2022), indicating their abuse potential.…”

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confidence: 99%

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Jones¹,

Huang²,

Manke³

et al. 2023

Experimental and Clinical Psychopharmacology

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Recently, use of the synthetic cathinone (aka "bath salt") eutylone has risen in the United States and globally. Due to its novelty in drug markets, its affective properties remain largely uninvestigated. In this context, drugs of abuse have both rewarding and aversive effects and understanding these effects, their relative balance, and factors that impact each are important to understanding the likelihood of drug use and abuse. This investigation attempted to characterize eutylone's rewarding and aversive effects in a combined conditioned taste avoidance/place preference assay. Female Sprague-Dawley rats were given 20-min access to saccharin, injected with one of five doses of eutylone (0, 3, 10, 18, 32 mg/kg; intraperitoneally; IP), and placed on one side of a place conditioning apparatus. On the following day, subjects were given 20-min access to water, injected IP with vehicle, and placed on the other side of the apparatus. After five conditioning cycles, place preference and saccharin avoidance were assessed. Eutylone induced significant taste avoidance but did not significantly increase time spent on the drug-paired side (relative to controls). Excluding animals with high initial side preference, however, eutylone induced a preference at all doses with the high dose group displaying higher preference than controls. There was no significant correlation between eutylone's aversive and rewarding effects. These data indicate that eutylone (like other synthetic cathinones) induces both rewarding and aversive effects and highlight the need to assess the impact of various factors on its affective properties (and their balance) and on their use and abuse. Public Health SignificanceThis study is the first to demonstrate taste avoidance and place preference induced by the novel synthetic cathinone eutylone. Given that a drug's aversive and rewarding effects are thought in balance to mediate its use and abuse, the present study indicates the potential abuse of eutylone and the importance in assessing various factors that could affect this liability.

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“…All rats were housed in a temperature- and humidity-controlled room on a 12 h light/dark cycle with food and water available ad libitum. Alcohol-dependent rats (average blood alcohol level 172.68 ± 17.4 mg/dL at time of sacrifice) were generated by exposure to alcohol vapor daily (14 h alcohol vapor; 10 h air vapor) for 5–7 weeks [ 30 , 48 , 49 , 50 ] Female ( N = 6) and male ( N = 6) Wistar rats (Charles River, Raleigh, NC, USA) weighed on average 253.17 ± 12.7 g and 387.67 ± 24.5 g, respectively, at time of sacrifice. All procedures and care were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were reviewed and approved by the Institutional Animal Care and Use Committee of The Scripps Research Institute.…”

Section: Methodsmentioning

confidence: 99%

Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses

Rodriguez

Kirson

Wolfe

et al. 2022

IJMS

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Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by the recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin-releasing factor (CRF)-CRF1 receptor and Gamma-Aminobutyric Acid (GABA)-ergic signaling dysregulation occurring in alcohol-dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch-clamp electrophysiology to examine the effects of alcohol dependence on the CRF modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared to males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had fewer CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike in males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

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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

Cited by 6 publications

References 67 publications

Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain

Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses

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