High affinity [3H]zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors

Arbilla, S.; Allen, John G.; Wick, A. K.; Langer, Salomón Z.

doi:10.1016/0014-2999(86)90276-1

Cited by 107 publications

(34 citation statements)

References 23 publications

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“…Receptors containing the a1 subunit exhibit BZ 1 receptor pharmacology, with a high affinity for classical BZ agonists, such as diazepam and alprazolam, and also for the atypical BZ agonists, CL218872 and zolpidem. Transfection studies of recombinant GABA A receptors comprised of a1, b, g1, or g2 subunits exhibit BZ 1 receptor pharmacology, with highaffinity binding for zolpidem (Barnard et al, 1988;Mehta and Ticku, 1999), which binds BZ 1 receptors with an affinity (k d B7 nM) that is at least 20 times greater than for BZ 2 receptors (Arbilla et al, 1986). Receptors composed of the a2, a3, or a5 subunits show BZ 2 receptor profiles, with high affinity for classical BZ agonists, but greatly reduced affinity for zolpidem.…”

Section: Discussionmentioning

confidence: 99%

Variations in Maternal Care Alter GABAA Receptor Subunit Expression in Brain Regions Associated with Fear

Caldji

Diorio

Meaney

2003

Neuropsychopharmacol

214

164

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Maternal care influences the development of stress reactivity in the offspring. These effects are accompanied by changes in corticotropinreleasing factor (CRF) expression in brain regions that regulate responses to stress. However, such effects appear secondary to those involving systems that normally serve to inhibit CRF expression and release. Thus, maternal care over the first week of life alters GABA A (gamma-aminobutyric acid) A receptor mRNA subunit expression. The adult offspring of mothers that exhibit increased levels of pup licking/grooming and arched back-nursing (high LG-ABN mothers) show increased a1 mRNA levels in the medial prefrontal cortex, the hippocampus as well as the basolateral and central regions, of the amygdala and increased g2 mRNA in the amygdala. Western blot analyses confirm these effects at the level of protein. In contrast, the offspring of low LG-ABN mothers showed increased levels of a3 and a4 subunit mRNAs. The results of an adoption study showed that the biological offspring of low LG-ABN mothers fostered shortly after birth to high LG-ABN dams showed the increased levels of both a1 and g2 mRNA expression in the amygdala in comparison to peers fostered to other low LG-ABN mothers (the reverse was true for the biological offspring of high LG-ABN mothers). These findings are consistent with earlier reports of the effects of maternal care on GABA A /benzodiazepine receptor binding and suggest that maternal care can permanently alter the subunit composition of the GABA A receptor complex in brain regions that regulate responses to stress.

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Section: Discussionmentioning

confidence: 99%

Variations in Maternal Care Alter GABAA Receptor Subunit Expression in Brain Regions Associated with Fear

Caldji

Diorio

Meaney

2003

Neuropsychopharmacol

214

164

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“…Even if its effect seemed to be weaker than that of 5 mg/kg DZ, we cannot directly compare the efficacy of the two drugs to induce a long-lasting neurobiological change when using only one dose. Although the affinities of ZOL and DZ for the a1 subunit-containing receptors might be similar or differ slightly (about twofold) in recombinant a1b2/3g2 GABA A receptors (Wieland and Lüddens, 1994;Atack et al, 1999) and in a1 subunit-enriched regions of the rat brain (Arbilla et al, 1986;Benavides et al, 1988), the most important difference might be in the time course of action. ZOL is a short-acting hypnotic, with in vivo occupancy of the GABA A receptor BZ sites lasting only about 15-30 min after i.p.…”

Section: Discussionmentioning

confidence: 99%

Long-lasting Modulation of Glutamatergic Transmission in VTA Dopamine Neurons after a Single Dose of Benzodiazepine Agonists

Heikkinen

Möykkynen

Korpi

2008

Neuropsychopharmacol

103

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Initial effects of drugs of abuse seem to converge on the mesolimbic dopamine pathway originating from the ventral tegmental area (VTA). Even after a single dose, many drugs of abuse are able to modulate the glutamatergic transmission activating the VTA dopamine neurons, which may represent a critical early stage in the development of addiction. Ligands acting on the benzodiazepine site of the inhibitory g-aminobutyric acid type A (GABA A ) receptors are known to be rewarding in animal models and have abuse liability in humans, but notably little evidence exists on the involvement of the mesolimbic dopamine system in their effects. Here we report that single in vivo doses of benzodiazepine-site agonists, similar to morphine and ethanol, induce a modulation in the glutamatergic transmission of VTA dopamine neurons. This is seen 24 h later as an increase in the ratio between a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated excitatory currents using whole-cell patch-clamp configuration in mouse VTA slices. The effect was due to increased frequency of spontaneous miniature AMPA receptor-mediated currents. It lasted at least 3 days after the injection of diazepam, and was prevented by coadministration of the benzodiazepine-site antagonist flumazenil or the NMDA receptor antagonist dizocilpine. A single injection of the GABA A receptor a1 subunit-preferring benzodiazepine-site ligand zolpidem also produced an increase in the AMPA/NMDA ratio in VTA dopamine neurons. These findings suggest a role for the mesolimbic dopamine system in the initial actions of and on neuronal adaptation to benzodiazepines.

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“…Based on their affinity for different drugs, two different benzodiazepine binding sites have been identified in the central nervous system. Type I (benzodiazepine receptor 1, 1 ) displays high affinity for CL 218,872 (2), ␤-carboline derivates (3), and the imidazopyridine zolpidem (4,5). Type II (benzodiazepine receptor 2, 2 ) displays low affinity for these compounds.…”

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confidence: 99%

Molecular and Pharmacological Characterization of Native Cortical γ-Aminobutyric AcidA Receptors Containing Both α1 and α3 Subunits

Araujo

Tan²,

Ruano

et al. 1996

Journal of Biological Chemistry

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High affinity [3H]zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors

Cited by 107 publications

References 23 publications

Variations in Maternal Care Alter GABAA Receptor Subunit Expression in Brain Regions Associated with Fear

Variations in Maternal Care Alter GABAA Receptor Subunit Expression in Brain Regions Associated with Fear

Long-lasting Modulation of Glutamatergic Transmission in VTA Dopamine Neurons after a Single Dose of Benzodiazepine Agonists

Molecular and Pharmacological Characterization of Native Cortical γ-Aminobutyric AcidA Receptors Containing Both α1 and α3 Subunits

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