Quantification of Ten Neuroactive Steroids in Plasma in Withdrawal Seizure-Prone and -Resistant Mice During Chronic Ethanol Withdrawal

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2014 May 30

PMID 24871700

Citations 18

Authors

Christopher Snelling

Michelle A Tanchuck-Nipper

Matthew M Ford

Jeremiah P Jensen

Debra K Cozzoli

Marcia J Ramaker

Melinda Helms

John C Crabbe

David J Rossi

Deborah A Finn

Affiliations

Soon will be listed here.

Abstract

Rationale: The rapid membrane actions of neuroactive steroids, particularly via an enhancement of γ-aminobutyric acidA receptors (GABAARs), participate in the regulation of central nervous system excitability. Prior evidence suggests an inverse relationship between endogenous GABAergic neuroactive steroid levels and behavioral changes in excitability during ethanol withdrawal.

Objectives: Previously, we found that ethanol withdrawal significantly decreased plasma allopregnanolone (ALLO) levels, a potent GABAergic neuroactive steroid, and decreased GABAAR sensitivity to ALLO in Withdrawal Seizure-Prone (WSP) but not in Withdrawal Seizure-Resistant (WSR) mice. However, the effect of ethanol withdrawal on levels of other endogenous GABAAR-active steroids is not known.

Methods: After validation of a gas chromatography-mass spectrometry method for the simultaneous quantification of ten neuroactive steroids, we analyzed plasma from control male WSP-1 and WSR-1 mice and during ethanol withdrawal.

Results: We quantified levels of nine neuroactive steroids in WSP-1 and WSR-1 plasma; levels of pregnanolone were not detectable. Basal levels of five neuroactive steroids were higher in WSR-1 versus WSP-1 mice. Ethanol withdrawal significantly suppressed five neuroactive steroids in WSP-1 and WSR-1 mice, including ALLO.

Conclusions: Due to lower basal levels of some GABAAR-active steroids in WSP-1 mice, a withdrawal-induced decrease in WSP-1 mice may have a greater physiological consequence than a similar decrease in WSR-1 mice. Because WSP-1 mice also exhibit a reduction in GABAAR sensitivity to neuroactive steroids during withdrawal, it is possible that the combined decrease in neuroactive steroids and GABAAR sensitivity during ethanol withdrawal in WSP-1 mice represents a neurochemical substrate for severe ethanol withdrawal.

Citing Articles

Luteal phase sertraline treatment of premenstrual dysphoric disorder (PMDD): Effects on markers of hypothalamic pituitary adrenal (HPA) axis activation and inflammation.

Barone J, Ho A, Osborne L, Eisenlohr-Moul T, Morrow A, Payne J Psychoneuroendocrinology. 2024; 169:107145.

PMID: 39096755 PMC: 11381144. DOI: 10.1016/j.psyneuen.2024.107145.

Acute, but not repeated, cocaine exposure alters allopregnanolone levels in the midbrain of male and female rats.

McFarland M, Machado M, Sansbury G, Musselman K, Boero G, OBuckley T Psychopharmacology (Berl). 2024; 241(5):1011-1025.

PMID: 38282126 PMC: 11180476. DOI: 10.1007/s00213-024-06534-8.

GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder.

Miller K, Standeven L, Morrow A, Payne J, Epperson C, Hantsoo L Psychoneuroendocrinology. 2023; 160:106684.

PMID: 38091917 PMC: 10846389. DOI: 10.1016/j.psyneuen.2023.106684.

Stress and gonadal steroid influences on alcohol drinking and withdrawal, with focus on animal models in females.

Finn D Front Neuroendocrinol. 2023; 71:101094.

PMID: 37558184 PMC: 10840953. DOI: 10.1016/j.yfrne.2023.101094.

Pharmacological administration of 3α,5α-THP into the nucleus accumbens core increases 3α,5α-THP expression and reduces alcohol self-administration.

Ornelas L, Boero G, Van Voorhies K, OBuckley T, Besheer J, Morrow A Alcohol Clin Exp Res (Hoboken). 2023; 47(3):459-469.

PMID: 36587947 PMC: 10234128. DOI: 10.1111/acer.15008.

References

Purdy R, Morrow A, Blinn J, Paul S . Synthesis, metabolism, and pharmacological activity of 3 alpha-hydroxy steroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes. J Med Chem. 1990; 33(6):1572-81. DOI: 10.1021/jm00168a008. View

Sierksma A, Sarkola T, Eriksson C, van der Gaag M, Grobbee D, Hendriks H . Effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate, testosterone, and estradiol levels in middle-aged men and postmenopausal women: a diet-controlled intervention study. Alcohol Clin Exp Res. 2004; 28(5):780-5. DOI: 10.1097/01.alc.0000125356.70824.81. View

Liang J, Cagetti E, Olsen R, Spigelman I . Altered pharmacology of synaptic and extrasynaptic GABAA receptors on CA1 hippocampal neurons is consistent with subunit changes in a model of alcohol withdrawal and dependence. J Pharmacol Exp Ther. 2004; 310(3):1234-45. DOI: 10.1124/jpet.104.067983. View

Finn D, Ford M, Wiren K, Roselli C, Crabbe J . The role of pregnane neurosteroids in ethanol withdrawal: behavioral genetic approaches. Pharmacol Ther. 2004; 101(2):91-112. DOI: 10.1016/j.pharmthera.2003.10.006. View

Finn D, Douglass A, Beadles-Bohling A, Tanchuck M, Long S, Crabbe J . Selected line difference in sensitivity to a GABAergic neurosteroid during ethanol withdrawal. Genes Brain Behav. 2006; 5(1):53-63. DOI: 10.1111/j.1601-183X.2005.00137.x. View

McKeon A, Frye M, Delanty N . The alcohol withdrawal syndrome. J Neurol Neurosurg Psychiatry. 2007; 79(8):854-62. DOI: 10.1136/jnnp.2007.128322. View

Martinez-Riera A, Santolaria-Fernandez F, Gonzalez Reimers E, Milena A, Gomez-Sirvent J, Rodriguez-Moreno F . Alcoholic hypogonadism: hormonal response to clomiphene. Alcohol. 1995; 12(6):581-7. DOI: 10.1016/0741-8329(95)02006-3. View

Finn D, Crabbe J . Chronic ethanol differentially alters susceptibility to chemically induced convulsions in withdrawal seizure-prone and -resistant mice. J Pharmacol Exp Ther. 1999; 288(2):782-90. View

Crabbe J, Kosobud A, Young E, Tam B, McSwigan J . Bidirectional selection for susceptibility to ethanol withdrawal seizures in Mus musculus. Behav Genet. 1985; 15(6):521-36. DOI: 10.1007/BF01065448. View

10.

Alomary A, Fitzgerald R, Purdy R . Neurosteroid analysis. Int Rev Neurobiol. 2001; 46:97-115. DOI: 10.1016/s0074-7742(01)46060-0. View

11.

Tanchuck M, Long S, Ford M, Hashimoto J, Crabbe J, Roselli C . Selected line difference in the effects of ethanol dependence and withdrawal on allopregnanolone levels and 5alpha-reductase enzyme activity and expression. Alcohol Clin Exp Res. 2009; 33(12):2077-87. PMC: 2789917. DOI: 10.1111/j.1530-0277.2009.01047.x. View

12.

Liang J, Zhang N, Cagetti E, Houser C, Olsen R, Spigelman I . Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors. J Neurosci. 2006; 26(6):1749-58. PMC: 6793625. DOI: 10.1523/JNEUROSCI.4702-05.2006. View

13.

Rupprecht R, Holsboer F . Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. 1999; 22(9):410-6. DOI: 10.1016/s0166-2236(99)01399-5. View

14.

Devaud L, Risinger F, Selvage D . Impact of the hormonal milieu on the neurobiology of alcohol dependence and withdrawal. J Gen Psychol. 2006; 133(4):337-56. DOI: 10.3200/GENP.133.4.337-356. View

15.

Romeo E, Brancati A, De Lorenzo A, FUCCI P, Furnari C, Pompili E . Marked decrease of plasma neuroactive steroids during alcohol withdrawal. Clin Neuropharmacol. 1996; 19(4):366-9. DOI: 10.1097/00002826-199619040-00011. View

16.

Finn D, Gallaher E, Crabbe J . Differential change in neuroactive steroid sensitivity during ethanol withdrawal. J Pharmacol Exp Ther. 1999; 292(1):394-405. View

17.

Ylikahri R, Huttunen M, HARKONEN M . Hormonal changes during alcohol intoxication and withdrawal. Pharmacol Biochem Behav. 1980; 13 Suppl 1:131-7. DOI: 10.1016/s0091-3057(80)80021-9. View

18.

Ford M, Steele A, McCracken A, Finn D, Grant K . The relationship between adjunctive drinking, blood ethanol concentration and plasma corticosterone across fixed-time intervals of food delivery in two inbred mouse strains. Psychoneuroendocrinology. 2013; 38(11):2598-610. PMC: 3812349. DOI: 10.1016/j.psyneuen.2013.06.011. View

19.

Romeo E, Pompili E, Di Michele F, Pace M, Rupprecht R, Bernardi G . Effects of fluoxetine, indomethacine and placebo on 3 alpha, 5 alpha tetrahydroprogesterone (THP) plasma levels in uncomplicated alcohol withdrawal. World J Biol Psychiatry. 2003; 1(2):101-4. DOI: 10.3109/15622970009150572. View

20.

Belelli D, Lambert J . Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci. 2005; 6(7):565-75. DOI: 10.1038/nrn1703. View