Distribution of [3H]zolpidem binding sites in relation to messenger RNA encoding the α1, β2 and γ2 subunits of GABAA receptors in rat brain

Duncan, Gary E.; Breese, George R.; Criswell, Hugh E.; McCown, Thomas J.; Herbert, James S.; Devaud, Leslie L.; Morrow, A. Leslie

doi:10.1016/0306-4522(94)00433-6

Cited by 75 publications

(50 citation statements)

References 44 publications

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“…These findings are in excellent agreement with some mRNA studies of subunit distribution in the rat 3, 62 . However, in a study examining α1, β2, and γ2 transcript distribution, Duncan et al 17 reported intense α1 and β2 expression in the piriform cortex which is at odds with our findings.…”

Section: Comparison With Previous Mrna and Immunocytochemical Reportscontrasting

confidence: 99%

Forebrain and midbrain distribution of major benzodiazepine-sensitive GABAA receptor subunits in the adult C57 mouse as assessed with in situ hybridization

Heldt

Ressler

2007

Neuroscience

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In the adult brain, gamma-amino butyric acid (GABA) is the major inhibitory neurotransmitter. Understanding of the behavioral and pharmacological functions of GABA has been advanced by recent studies of mouse lines that possess mutations in various GABA receptor subtypes and associated proteins. Genetically altered mice have become important tools for discerning GABAergic function. Thus detailed knowledge of the anatomical distribution of different GABA A subtype receptors in mice is a prerequisite for understanding the neural circuitry underlying changes in normal and drug-induced behaviors seen in mutated mice. In the current study, we used in situ hybridization histochemistry with [35S]UTP-labeled riboprobes to examine the regional expression pattern of mRNA transcripts for 7 major GABA A receptor subunits in adjacent coronal brain sections (alpha 1, alpha 2, alpha 3, alpha 5, beta 2, beta 3, and gamma 2). Our results indicate that many of these GABAergic genes are co-expressed in much of the adult brain including the neocortex, hippocampus, amygdala, thalamus and striatum. However, each gene also shows a unique region-specific distribution pattern, indicative of distinct neuronal circuits that may serve specific physiological and pharmacological functions.

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Section: Comparison With Previous Mrna and Immunocytochemical Reportscontrasting

confidence: 99%

Forebrain and midbrain distribution of major benzodiazepine-sensitive GABAA receptor subunits in the adult C57 mouse as assessed with in situ hybridization

Heldt

Ressler

2007

Neuroscience

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“…For example, both contain primarily medium-sized spiny GABAergic neurons (Alheid and Heimer, 1988;McDonald, 1982) and both structures possess reciprocal dopaminergic innervation from midbrain tegmental areas (Freedman and Cassell, 1994;Gonzales and Chesselet, 1991). Second, the CPu is devoid of a 1 -and a 3 -containing GABA A receptors, but contains substantial levels of the a 2 isoform (Wisden et al, 1992;Duncan et al, 1995;Fritschy and Möhler, 1995). Third, the CPu contains substantial levels of m and d opiate receptors (Mansour et al, 1987(Mansour et al, , 1995McBride and Li, 1998).…”

Section: Discussionmentioning

confidence: 99%

GABAA and Opioid Receptors of the Central Nucleus of the Amygdala Selectively Regulate Ethanol-Maintained Behaviors

Foster

McKay

Seyoum

et al. 2003

Neuropsychopharmacol

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The present study tested the hypothesis that GABA A and opioid receptors within the central nucleus of the amygdala (CeA) regulate ethanol (EtOH), but not sucrose-maintained responding. To accomplish this, bCCt, a mixed benzodiazepine (BDZ) agonist-antagonist with binding selectivity at the a1 subunit-containing GABA A receptor, and the nonselective opioid antagonist, naltrexone, were bilaterally infused directly into the CeA of alcohol-preferring rats. The results demonstrated that in HAD-1 and P rat lines, bCCt (5-60 mg) reduced EtOH-maintained responding by 56-89% of control levels. On day 2, bCCt (10-40 mg) continued to suppress EtOH maintained responding in HAD-1 rats by as much as 60-85% of control levels. Similarly, naltrexone (0.5-30 mg) reduced EtOH-maintained responding by 56-75% of control levels in P rats. bCCt and naltrexone exhibited neuroanatomical and reinforcer specificity within the CeA. Specifically, no effects on EtOH-maintained responding were observed following infusion into the caudate putamen (CPu), a locus several millimeters dorsal to the CeA. Additionally, responding maintained by sucrose, when presented concurrently with ethanol (EtOH) or presented alone, was not altered by bCCt. Naltrexone reduced sucrose-maintained responding only under the 5 mg dose condition when sucrose was presented alone, however, it did not alter sucrose responding when given concurrently with EtOH. These results support the hypothesis that GABA A and opioid receptors within the CeA can selectively regulate EtOH-maintained responding. The CeA may represent a novel target site in the development of prototypical GABA A and opioidergic receptor ligands, which selectively reduce alcohol abuse in humans.

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“…This GABA A receptor combination (a 1 b X g 2 ) reportedly is the most abundant BZD/GABA A receptor in brain Lüddens and Korpi, 1995;Mckernan and Whiting, 1996). Binding of zolpidem, as a BZD-receptor agonist selective for GABA A receptors that contained a 1 b X g 2 receptor subunits (Wafford et al, 1993;Criswell et al, 1997), localized with the a 1 b 2 g 2 GABA A receptor subunit combination Duncan et al, 1995). Importantly, zolpidem binding was found in the medial septum, a site where muscimol increased ethanol-induced sedation, but not in the lateral septum, a site where muscimol did not have this action (Givens and Breese, 1990b;McCown et al, 1986).…”

Section: Hypothesis For Ethanol Action On a Type-1-bzd Receptormentioning

confidence: 99%

A Conceptualization of Integrated Actions of Ethanol Contributing to its GABAmimetic Profile: A Commentary

Criswell

Breese

2005

Neuropsychopharmacol

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Early behavioral investigations supported the contention that systemic ethanol displays a GABAmimetic profile. Microinjection of GABA agonists into brain and in vivo electrophysiological studies implicated a regionally specific action of ethanol on GABA function. While selectivity of ethanol to enhance the effect of GABA was initially attributed an effect on type-1-benzodiazepine (BZD)-GABA A receptors, a lack of ethanol's effect on GABA responsiveness from isolated neurons with this receptor subtype discounted this contention. Nonetheless, subsequent work identified GABA A receptor subtypes, with limited distribution in brain, sensitive to enhancement of GABA at relevant ethanol concentrations. In view of these data, it is hypothesized that the GABAmimetic profile for ethanol is due to activation of mechanisms associated with GABA function, distinct from a direct action on the majority of postsynaptic GABA A receptors. The primary action proposed to account for ethanol's regional specificity on GABA transmission is its ability to release GABA from some, but not all, presynaptic GABAergic terminals. As systemic administration of ethanol increases neuroactive steroids, which can enhance GABA responsiveness, this elevated level of neurosteroids is proposed to magnify the effect of GABA released by ethanol. Additional factors contributing to the degree to which ethanol interacts with GABA function include an involvement of GABA B and other receptors that influence ethanol-induced GABA release, an effect of phosphorylation on GABA responsiveness, and a regional reduction of glutamatergic tone. Thus, an integration of these consequences induced by ethanol is proposed to provide a logical basis for its in vivo GABAmimetic profile.

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Distribution of [3H]zolpidem binding sites in relation to messenger RNA encoding the α1, β2 and γ2 subunits of GABAA receptors in rat brain

Cited by 75 publications

References 44 publications

Forebrain and midbrain distribution of major benzodiazepine-sensitive GABAA receptor subunits in the adult C57 mouse as assessed with in situ hybridization

Forebrain and midbrain distribution of major benzodiazepine-sensitive GABAA receptor subunits in the adult C57 mouse as assessed with in situ hybridization

GABAA and Opioid Receptors of the Central Nucleus of the Amygdala Selectively Regulate Ethanol-Maintained Behaviors

A Conceptualization of Integrated Actions of Ethanol Contributing to its GABAmimetic Profile: A Commentary

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