Neurosteroids in Alcohol and Substance Use

Ginsburg, Brett C.; Gerak, Lisa R.; McMahon, Lance Richard; Roache, John D.

doi:10.1007/978-1-4020-6854-6_25

Cited by 3 publications

(2 citation statements)

References 146 publications

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“…P4 declines in the late luteal (premenstrual) phase may also directly motivate alcohol use. Alcohol and the neuroactive steroid metabolites of P4 (especially allopregnanolone, or ALLO) share GABAergic mechanisms of action (Ginsburg, Gerak, McMahon, & Roache, 2008; Torres & Ortega, 2003). Therefore, P4/ALLO declines might increase alcohol consumption as a method of compensating for decreased GABAergic activity, which may cause both aversive arousal and increased risk taking (Kiesner, 2012; Löfgren, Johansson, Meyerson, Lundgren, & Bäckström, 2006).…”

Section: Discussionmentioning

confidence: 99%

Interactive effects of ovarian steroid hormones on alcohol use and binge drinking across the menstrual cycle.

Martel¹,

Eisenlohr‐Moul²,

Roberts³

2017

Journal of Abnormal Psychology

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Patterns and features of substance use and abuse vary across the menstrual cycle in humans. Yet, little work has systematically examined the within-person relationships between ovarian hormone changes and alcohol use across the menstrual cycle. Our study was the first to examine the roles of within-person levels and changes in estradiol (E2) and progesterone (P4) in relation to daily alcohol use and binge drinking in young women. Participants were 22 naturally-cycling women, ages 18–22, recruited through a university subject pool who reported any alcohol use and who completed a screening visit assessing study eligibility, followed by 35 subsequent days of data collection. E2 and P4 were obtained via enzyme immunoassay of saliva samples collected by participants each morning, thirty minutes after waking. Presence and degree of daily substance use were obtained using an adaptation of the Timeline FollowBack Interview completed daily. Results indicated that elevated E2 in the context of decreased P4 levels were associated with higher risk of drinking and binge drinking. These effects were present only on weekend days. Results are suggestive of a dual risk model in which both ovulatory E2 increases and perimenstrual P4 decreases increase risk for drinking. Differential associations of steroids with drinking across the menstrual cycle may suggest the need for clinical assessment of substance use to take into account hormone dynamics and menstrual cycle phase.

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Section: Discussionmentioning

confidence: 99%

Interactive effects of ovarian steroid hormones on alcohol use and binge drinking across the menstrual cycle.

Martel¹,

Eisenlohr‐Moul²,

Roberts³

2017

Journal of Abnormal Psychology

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“…Exogenous allopregnanolone was shown to substitute for drugs due to reinforcing potential. 41,42 Involvement of neurosteroids in alcohol abuse, tolerance and withdrawal were correlated. There appears to be a time relationship between the behavioural effects of alcohol and the levels of alcohol-induced allopregnanolone in the brain.…”

Section: Alcohol and Other Substance Abusementioning

confidence: 99%

Neurosteroids: current perspective in therapy of neuropsychiatric disorders

Tolety¹,

Maity²,

Anuradha³

2019

Int J Basic Clin Pharmacol

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Neurosteroids are natural or synthetic steroid derivatives which act locally in brain by modulating neuronal excitability. The objective of this study is to analyze available literature on classification, biosynthesis and mechanism of action, and therapeutic potential of neurosteroids. A review of literature pertaining to neurosteroids published from inception to 2018 was carried on data bases like PUBMED, Google Scholar and Science Direct. The search terms used were neurosteroids, neuro-active steroids, ganaxolone and GABA-A receptor modulators. Review of literature suggests neurosteroids are powerful neuro-modulators, involving rapid non-genomic and non-hormone receptor mechanisms. They are classified based on structure as pregnane, androstane and sulphated neurosteroids, and based on function as excitatory or inhibitory neurosteroids. They act via GABAA receptor (primarily), rho- GABA (ρGABA), NMDA-glutamate and sigma receptor modulation. The inhibitory neurosteroids demonstrate sedative, anxiolytic and anticonvulsant actions, whereas the excitatory agents produce memory enhancing and anxiogenic effects. They show efficacy in various CNS and psychiatric conditions like epilepsy, anxiety, depression, learning and memory disorders and substance abuse. Endogenous neurosteroids have limited clinical use due to low bioavailability, lack of specificity and unwanted effects. Hence, synthetic agents like alphaxalone, ganaxolone, sepranolone and brexanolone which have better bioavailability and specificity, are being investigated in various phases of clinical trials. Neurosteroids are novel endogenous compounds with neuro-modulatory function and show promising effects in therapy of various neurological and psychiatric conditions. Further studies that prove their long term efficacy and safety may revolutionize the clinical approach to therapy of these conditions.

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Overlapping, but not identical, discriminative stimulus effects of the neuroactive steroid pregnanolone and ethanol

Gerak

Moerschbaecher

Winsauer

2008

Pharmacology Biochemistry and Behavior

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Many behavioral effects of neuroactive steroids are mediated by GABA(A) receptors; however, other receptors might be involved. Ethanol has a complex mechanism of action, and many of the same receptors have been implicated in the effects of neuroactive steroids and ethanol. The goal of this study was to determine whether actions of neuroactive steroids and ethanol at multiple receptors result in similar discriminative stimulus effects. Rats discriminated 5.6 mg/kg of pregnanolone while responding under a fixed-ratio 20 schedule of food presentation. Pregnanolone, flunitrazepam and pentobarbital produced >80% pregnanolone-lever responding. In contrast, neither morphine nor the negative GABA(A) modulator beta-CCE substituted for pregnanolone up to doses that markedly decreased response rates. Ethanol substituted only in some rats; in other rats, ethanol produced <20% pregnanolone-lever responding up to rate-decreasing doses. Thus, substitution of positive GABA(A) modulators, and not morphine or beta-CCE, for pregnanolone in all rats suggests that positive modulation of GABA(A) receptors is important in the discriminative stimulus effects of pregnanolone. Although pregnanolone might have actions at other receptors, in addition to actions at GABA(A) receptors, substitution of ethanol for pregnanolone only in some rats suggests that the mechanisms of action of pregnanolone and ethanol overlap, but are not identical.

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Neurosteroids in Alcohol and Substance Use

Cited by 3 publications

References 146 publications

Interactive effects of ovarian steroid hormones on alcohol use and binge drinking across the menstrual cycle.

Interactive effects of ovarian steroid hormones on alcohol use and binge drinking across the menstrual cycle.

Neurosteroids: current perspective in therapy of neuropsychiatric disorders

Overlapping, but not identical, discriminative stimulus effects of the neuroactive steroid pregnanolone and ethanol

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