Paradoxical widespread c-Fos expression induced by a GABA agonist in the forebrain of transgenic mice with ectopic expression of the GABA(A) α6 subunit.

A GABA-site agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) at 3 mg/kg induces strong anxiolytic response in a transgenic Thy1α6 mouse line ectopically expressing the GABA(A) receptor α6 subunit gene under the Thy-1.2 promoter. Now, we compared brain activation patterns between Thy1α6 and wild-type mice to identify brain structures potentially mediating this anxiolytic response.

Human locus coeruleus neurons express the GABA(A) receptor gamma2 subunit gene and produce benzodiazepine binding.

Noradrenergic neurons of the locus coeruleus project throughout the cerebral cortex and multiple subcortical structures. Alterations in the locus coeruleus firing are associated with vigilance states and with fear and anxiety disorders. Brain ionotropic type A receptors for gamma-aminobutyric acid (GABA) serve as targets for anxiolytic and sedative drugs, and play an essential regulatory role in the locus coeruleus.

Prototypic GABA(A) receptor agonist muscimol acts preferentially through forebrain high-affinity binding sites.

Muscimol has been regarded as a universal agonist for all gamma-aminobutyric acid type A receptor (GABA(A)-R) subtypes. However, brain regional distribution of muscimol's high-affinity binding sites greatly differs from those of other binding sites of the GABA(A)-R. To test whether behavioral effects of muscimol correlated with the density of high-affinity [(3)H]muscimol binding, we examined several GABA(A)-R subunit gene-modified mouse lines: alpha1, alpha4, or delta-knockouts (KO), alpha4+delta-double KO, and Thy1.

Conscious sedation by rectal administration of midazolam or midazolam plus ketamine as alternatives to general anesthesia for dental treatment of uncooperative children.

The trial included 24 children (aged 2-7 yr) referred for dental treatment under general anesthesia, since conventional behavioral management methods had failed to achieve treatment acceptance. As an alternative, they received, on two separate occasions with "identical" dental treatment, conscious sedation by rectal administration of either midazolam (0.3 mg/kg body weight (bwt)) or midazolam (0.