Changes in GABAA receptor γ2 subunit gene expression induced by long-term administration of oral contraceptives in rats

Follesa, Paolo; Porcu, Patrizia; Sogliano, Cristiana; Cinus, Monica; Biggio, Francesca; Mancuso, Luisa; Mostallino, Maria Cristina; Paoletti, Anna Maria; Purdy, R. H.; Biggio, Giovanni; Concas, Alessandra

doi:10.1016/s0028-3908(01)00187-3

Cited by 100 publications

(56 citation statements)

References 38 publications

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“…These data indicate that the potency of these drugs for enhancement of neurosteroid synthesis is greater in the cerebral cortex than in the periphery, and that the accumulation of neurosteroids in the brain is not simply a function of their plasma concentrations. Differential regulation of neurosteroid concentrations between plasma and the brain has previously been suggested on the basis of the effects of various pharmacological treatments (Concas et al 2000;Barbaccia et al 2001;Follesa et al 2002) or physiological conditions (Concas et al 1998). Moreover, an ethanol-induced increase in de novo neurosteroid synthesis in the , and allopregnanolone (c) in the cerebral cortex of rats subjected to spontaneous withdrawal or naloxone-precipitated withdrawal from chronic treatment with morphine.…”

Section: Discussionmentioning

confidence: 99%

Neurosteroids in nicotine and morphine dependence

et al. 2005

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Changes in neurosteroid concentrations mediated by activation of the HPA axis may both contribute to the early acquisition phase of nicotine or morphine addiction and serve to counteract the anxiety-like behavior associated with nicotine or morphine withdrawal. However, the evidence that nicotine withdrawal did not increase neurosteroids, unless precipitated by mecamylamine, suggests that the role of these neurosteroids in spontaneous nicotine withdrawal may not be clear.

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Section: Discussionmentioning

confidence: 99%

Neurosteroids in nicotine and morphine dependence

et al. 2005

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“…Increased circulating levels of 3α,5α-THP have been reported during the luteal phase of the menstrual cycle in women (Wang et al 1996), and fluctuations in neuroactive steroid concentrations across the menstrual cycle correlate with symptoms of premenstrual dysphoric disorder (Girdler et al 2001; Wang et al 1996). Interestingly, treatment with hormonal contraceptives decreases plasma neuroactive steroids and prevents the increase in 3α,5α-THP during the luteal phase in women (Follesa et al 2002; Rapkin et al 2006). The same treatment also dramatically decreased brain 3α,5α-THP and progesterone concentrations, altered GABA A receptor subunit expression and induced anxiety-like behavior in female Sprague-Dawley rats (Follesa et al 2002; Porcu et al 2012).…”

Section: Physiological Regulation Of Neuroactive Steroid Levels In Plmentioning

confidence: 99%

“…Interestingly, treatment with hormonal contraceptives decreases plasma neuroactive steroids and prevents the increase in 3α,5α-THP during the luteal phase in women (Follesa et al 2002; Rapkin et al 2006). The same treatment also dramatically decreased brain 3α,5α-THP and progesterone concentrations, altered GABA A receptor subunit expression and induced anxiety-like behavior in female Sprague-Dawley rats (Follesa et al 2002; Porcu et al 2012). …”

Section: Physiological Regulation Of Neuroactive Steroid Levels In Plmentioning

confidence: 99%

Divergent neuroactive steroid responses to stress and ethanol in rat and mouse strains: relevance for human studies

Porcu

Morrow

2014

Psychopharmacology

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Rationale Neuroactive steroids are endogenous or synthetic steroids that rapidly alter neuronal excitability via membrane receptors, primarily GABAA receptors. Neuroactive steroids regulate many physiological processes including hypothalamic-pituitary-adrenal (HPA) axis function, ovarian cycle, pregnancy, aging, and reward. Moreover, alterations in neuroactive steroid synthesis are implicated in several neuropsychiatric disorders. Objectives This review will summarize the pharmacological properties and physiological regulation of neuroactive steroids, with a particular focus on divergent neuroactive steroid responses to stress and ethanol in rats, mice and humans. Results GABAergic neuroactive steroids exert a homeostatic regulation of the HPA axis in rats and humans, whereby the increase in neuroactive steroid levels following acute stress counteracts HPA axis hyperactivity and restores homeostasis. In contrast, in C57BL/6J mice, acute stress decreases neurosteroidogenesis and neuroactive steroids exert paradoxical excitatory effects upon the HPA axis. Rats, mice and humans also differ in the neuroactive steroid responses to ethanol. Genetic variation in neurosteroidogenesis may explain the different neuroactive steroid responses to stress or ethanol. Conclusions Rats and mouse strains show divergent effects of stress and ethanol on neuroactive steroids in both plasma and brain. The study of genetic variation in the various processes that determine neuroactive steroids levels as well as their effects on cell signaling may underlie these differences and may play a relevant role for the potential therapeutic benefits of neuroactive steroids.

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“…Changes in sensitivity of GABA A receptors toward allopregnanolone, due to alterations in subunit composition, are induced by neurosteroid withdrawal (Biggio et al, 2006;Gulinello et al, 2002;Mascia et al, 2002;Smith et al, 1998), long term steroid administration (Follesa et al, 2002) and in animal models of epilepsy (Banerjee et al, 1998;Brussaard and Herbison, 2000;Cagetti et al, 2003;Devaud et al, 1996;Follesa et al, 2000;Gulinello et al, 2002;Mtchedlishvili et al, 2001;Reddy and Rogawski, 2000), as well as to changes in neurosteroid concentrations resulting from pregnancy (Concas et al, 1998;Fujii and Mellon, 2001;Herbison, 2001), stress (Barbaccia et al, 1996), social isolation (Pinna et al, 2004;Serra et al, 2000), as well as due to age of the animal (Shen et al, 2007) …”

Section: Gaba a Receptor Sensitivity To Allopregnanolone During Develmentioning

confidence: 99%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

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Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

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Changes in GABAA receptor γ2 subunit gene expression induced by long-term administration of oral contraceptives in rats

Cited by 100 publications

References 38 publications

Neurosteroids in nicotine and morphine dependence

Neurosteroids in nicotine and morphine dependence

Divergent neuroactive steroid responses to stress and ethanol in rat and mouse strains: relevance for human studies

Neurosteroid regulation of central nervous system development

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