Patterns of mRNA and protein expression for 12 GABAA receptor subunits in the mouse brain

Hörtnagl, Heide; Tasan, Ramon; Wieselthaler, Anna; Kirchmair, Elke; Sieghart, Werner; Sperk, Günther

doi:10.1016/j.neuroscience.2013.01.008

Cited by 214 publications

(248 citation statements)

References 42 publications

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“…It has been shown that the D1-and D2-expressing MSNs have opposite effects on behavioral sensitization to and the development of conditioned place preference to cocaine (Lobo et al, 2010). Dense staining in earlier studies (Fritschy and Mohler 1995;Hörtnagl et al, 2013;Pirker et al, 2000) and our immunohistochemical analysis of the virally-infected cells in wild-type mice suggest that a large population of MSNs in the NAc expresses a2GABA A Rs. D2-positive MSNs project to the VP (Smith et al, 2013), which in turn sends GABAergic projections onto the VTA (Kalivas et al, 1993), at least partially onto GABAergic interneurons (Kaufling et al, 2009).…”

Section: Discussionmentioning

confidence: 53%

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Engin

Bakhurin

Smith

et al. 2014

Neuropsychopharmacol

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Despite long-standing concerns regarding the abuse liability of benzodiazepines, the mechanisms underlying properties of benzodiazepines that may be relevant to abuse are still poorly understood. Earlier studies showed that compounds selective for a1-containing GABA A receptors (a1GABA A Rs) are abused by humans and self-administered by animals, and that these receptors may underlie a preference for benzodiazepines as well as neuroplastic changes observed in the ventral tegmental area following benzodiazepine administration. There is some evidence, however, that even L-838, 417, a compound with antagonistic properties at a1GABA A Rs and agonistic properties at the other three benzodiazepine-sensitive GABA A receptor subtypes, is self-administered, and that the a2GABA A Rs may have a role in benzodiazepine-induced reward enhancement. Using a two-bottle choice drinking paradigm to evaluate midazolam preference and an intracranial self-stimulation (ICSS) paradigm to evaluate the impact of midazolam on reward enhancement, we demonstrated that mice carrying a histidine-to-arginine point mutation in the a2 subunit which renders it insensitive to benzodiazepines (a2(H101R) mice) did not prefer midazolam and did not show midazolam-induced reward enhancement in ICSS, in contrast to wild-type controls, suggesting that a2GABA A Rs are necessary for the reward enhancing effects and preference for oral benzodiazepines. Through a viral-mediated knockdown of a2GABA A Rs in the nucleus accumbens (NAc), we demonstrated that a2 in the NAc is necessary for the preference for midazolam. Findings imply that a2GABA A Rs in the NAc are involved in at least some rewardrelated properties of benzodiazepines, which might partially underlie repeated drug-taking behavior.

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Section: Discussionmentioning

confidence: 53%

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Engin

Bakhurin

Smith

et al. 2014

Neuropsychopharmacol

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“…In some cells expression of more than eight different isoforms has been demonstrated [5]. Throughout the CNS some subunits are broadly expressed, while others exhibit more restricted expression profile [17,18]. For example, the most abundant α1 subunit is expressed almost ubiquitously in the brain, α5 is highly expressed in the hippocampus, α6 subunit is expressed only in granule cells of the cerebellum, while ρ-subunits, the major molecular components of the formerly called GABAC receptors, are expressed mainly in the retina [19][20][21][22].…”

Section: Gabaa Receptors and Their Subunitsmentioning

confidence: 99%

GABA Receptors: Pharmacological Potential and Pitfalls

Jembrek¹,

Vlainić

2015

CPD

115

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Gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the mammalian central nervous system, plays a key role in the regulation of neuronal transmission throughout the brain, affecting numerous physiological and psychological processes. Changes in GABA levels provoke disbalance between excitatory and inhibitory signals, and are involved in the development of numerous neuropsychiatric disorders. GABA exerts its effects via ionotropic (GABAA) and metabotropic (GABAB) receptors. Both types of receptors are targeted by many clinically important drugs that affect GABAergic function and are widely used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, aggressive behaviour, and other pathophysiological conditions and diseases. Of particular importance are drugs that modulate GABAA receptor complex, such as benzodiazepines, barbiturates, neuroactive steroids, intravenous and inhalational anesthetics, and ethanol. Molecular interactions and subsequent pharmacological effects induced by drugs acting at GABAA receptors are extremely complex due to structural heterogeneity of GABAA receptors and existence of numerous allosterically interconnected binding sites and various chemically distinct ligands that are able to bound to them. There is a growing interest in the development and application of subtype-selective drugs that will achieve specific therapeutic benefits without undesirable side effects. The aim of this review is to briefly summarize the key pharmacological properties of GABA receptors, and to present selected novel findings with the potential to open new perspectives in the development of more effective therapeutic strategies.

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“…Recent immunohistochemical and electrophysiological data demonstrated the expression of ␣1-and ␦-subunits in the CeAm in mice (Herman et al 2013). Because there is evidence that the expression of the ␣1-subunit is much lower in CeAl compared with CeAm (Hortnagl et al 2013) and because the GABA A R ␦-subunit is the main target of neurosteroid action, we focused on this subunit.…”

Section: Tonic Inhibitory Transmission Is Present In Cea Neuronsmentioning

confidence: 99%

Neurosteroids increase tonic GABAergic inhibition in the lateral section of the central amygdala in mice

Romo-Parra

Blaesse

Sosulina

et al. 2015

Journal of Neurophysiology

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Patterns of mRNA and protein expression for 12 GABAA receptor subunits in the mouse brain

Abstract: Graphical abstractHighlights► The distribution of GABAA receptor subunits is highly heterogeneous. ► The distribution of mRNAs corresponds to that of proteins. ► The distribution in the mouse correlates largely to that in rats although there are distinct differences.

Cited by 214 publications

References 42 publications

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

GABA Receptors: Pharmacological Potential and Pitfalls

Neurosteroids increase tonic GABAergic inhibition in the lateral section of the central amygdala in mice

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