Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats

Khom, Sophia; Rodriguez, Larry; Gandhi, Pauravi J.; Kirson, Dean; Bajo, Michal; Christopher, S. Oleata; Leandro, F. Vendruscolo; Barbara, J. Mason; Roberto, Marisa

doi:10.1016/j.nbd.2022.105610

Cited by 13 publications

(10 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an effort to gain initial mechanistic information, we tested the effects of semaglutide on GABAergic synaptic transmission in the CeA and ILC — 2 brain areas critically involved in alcohol-related behaviors ( 28 , 29 , 101 , 102 ). We found that semaglutide induced an increase in both CeA and ILC GABA transmission in alcohol-naive rats.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, we found that semaglutide increased network-dependent GABA release in a small subset of cells, while it decreased it in the remaining cells, resulting in an average of no effect of semaglutide on GABAergic synapses in the context of alcohol dependence. Elevated GABAergic signaling in the CeA following chronic alcohol exposure is observed across multiple species ( 28 , 33 , 108 , 109 ), and reducing the heightened GABAergic tone in the CeA is a common denominator of various drugs that suppress alcohol consumption ( 101 , 110 , 111 ). Based on the present electrophysiology data, we can only speculate potential mechanisms underlying the mixed effects of GLP-1R activation on CeA and ILC GABA transmission in the alcohol-dependent animals.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission

Chuong,

Farokhnia,

Khom

et al. 2023

JCI Insight

Self Cite

View full text Add to dashboard Cite

Growing evidence indicates that the glucagon-like peptide-1 (GLP-1) system is involved in the neurobiology of addictive behaviors, and GLP-1 analogues may be used for the treatment of alcohol use disorder (AUD). Here, we examined the effects of semaglutide, a long-acting GLP-1 analogue, on biobehavioral correlates of alcohol use in rodents. A drinking-in-the-dark procedure was used to test the effects of semaglutide on binge-like drinking in male and female mice. We also tested the effects of semaglutide on binge-like and dependence-induced alcohol drinking in male and female rats, as well as acute effects of semaglutide on spontaneous inhibitory postsynaptic currents (sIPSCs) from central amygdala (CeA) and infralimbic cortex (ILC) neurons. Semaglutide dose-dependently reduced binge-like alcohol drinking in mice; a similar effect was observed on the intake of other caloric/noncaloric solutions. Semaglutide also reduced binge-like and dependence-induced alcohol drinking in rats. Semaglutide increased sIPSC frequency in CeA and ILC neurons from alcohol-naive rats, suggesting enhanced GABA release, but had no overall effect on GABA transmission in alcohol-dependent rats. In conclusion, the GLP-1 analogue semaglutide decreased alcohol intake across different drinking models and species and modulated central GABA neurotransmission, providing support for clinical testing of semaglutide as a potentially novel pharmacotherapy for AUD.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission

Chuong,

Farokhnia,

Khom

et al. 2023

JCI Insight

Self Cite

View full text Add to dashboard Cite

show abstract

“…Individuals initially drink alcohol primarily because of its pleasurable effects, but excessive drinking over time can result in the development of alcohol dependence and alcohol use disorder [ 1 ]. Alcohol dependence is a chronic relapsing disorder that is characterized by compulsive alcohol drinking with a concomitant loss of control over alcohol intake and negative emotional state when absent [ [2] , [3] , [4] ]. It has been reported that 53.6% of men and 32.3% of women aged 15 or older in the world consumed alcohol in 2016, and more than 200 health conditions are associated with harmful use of alcohol, including learning and memory impairment, cognitive impairment and depression [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The effect of chronic alcohol exposure on spatial memory and BDNF–TrkB- PLCγ1 signaling in the hippocampus of male and female mice

Feng

et al. 2023

Heliyon

View full text Add to dashboard Cite

“…Preparation of acute brain slices and electrophysiological recordings were performed as previously described [ 17 , 30 , 51 , 52 ]. Rats were deeply anesthetized with isoflurane (3–5%) before decapitation and brain isolation.…”

Section: Methodsmentioning

confidence: 99%

Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses

Rodriguez

Kirson

Wolfe

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats

Cited by 13 publications

References 71 publications

The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission

The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission

The effect of chronic alcohol exposure on spatial memory and BDNF–TrkB- PLCγ1 signaling in the hippocampus of male and female mice

Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses

Contact Info

Product

Resources

About