Cognitive impairment in Down syndrome (DS) is characterized by deficient learning and memory. Mouse genetic models of DS exhibit impaired cognition in hippocampally mediated behavioral tasks and reduced synaptic plasticity of hippocampal pathways. Enhanced efficiency of GABAergic neurotransmission was implicated in those changes. We have recently shown that signaling through postsynaptic GABA(B...

1) chronic administration of morphine hydrochloride in the drinking water of mice induced physical dependence. jumping and diarrhea, two signs of withdrawal, were produced by intraperitoneal (ip) injection of naloxone. 2) baclofen, bicuculline and picrotoxin decreased the number of mice's jumping episodes and frequency of diarrhea. 3) muscimol decreased jumping but not diarrhea. 4) the data ind...

The relationship between postsynaptic inhibitory responses [the fast GABA(A)-mediated inhibitory postsynaptic potential (IPSP) and the slow GABA(B)-mediated IPSP] were investigated in hippocampal CA3 pyramidal cells. Mossy fiber-evoked GABA(B)-mediated IPSPs were, paradoxically, of greater amplitude in cells with resting membrane potential of -62 mV (13.6 +/- 0.5 mV; mean +/- SE) as compared wi...

PURPOSE To learn whether gamma-aminobutyric acid (GABA) participates in retinal mechanisms that influence refractive development. METHODS White leghorn chicks, some of which wore a unilateral goggle to induce myopia, received daily intravitreal injections of agonists or antagonists to the major GABA receptor subtypes. Eyes were studied with refractometry, ultrasound, and calipers. Retinas of ...

The amygdala is intimately involved in emotional behavior, and its role in the generation of anxiety and conditioned fear is well known. Benzodiazepines, which are commonly used for the relief of anxiety, are thought to act by enhancing the action of the inhibitory transmitter GABA. We have examined the properties of GABA-mediated inhibition in the amygdala. Whole-cell recordings were made from...

The convulsant alkaloid bicuculline continues to be investigated more than 40 years after the first publication of its action as an antagonist of receptors for the inhibitory neurotransmitter GABA. This historical perspective highlights key aspects of the discovery of bicuculline as a GABA antagonist and the sustained interest in this and other GABA antagonists. The exciting advances in the mol...

There is an emerging body of data purporting a role of gamma-aminobutyric acid (GABA) in the pathophysiology of mood disorders. However, the role of metabotropic GABA(B) receptors in depression is not well defined. The modified forced swim test has recently emerged as an excellent tool to assess behaviorally the role of monoamines in antidepressant action. To assess the role of GABA(B) receptor...

GABA(B) receptors are unique among G-protein-coupled receptors (GPCRs) in their requirement for heterodimerization between two homologous subunits, GABA(B1) and GABA(B2), for functional expression. Whereas GABA(B1) is capable of binding receptor agonists and antagonists, the role of each GABA(B) subunit in receptor signaling is unknown. Here we identified amino acid residues within the second i...

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate brain. GABA activates both ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors in mammals. Whether non-mammalian vertebrates possess receptors with similar characteristics is not well understood. We used a mammalian GABA(B)-specific antagonist to determine the pharmacology of putative receptors in the...

The present study was designed to investigate the involvement of opioidergic component as well as to study GABAergic mechanisms in the expression of heroin discrimination. Male Wistar rats were trained to discriminate heroin (0.5 mg/kg, i.p.) from saline (i.p.) in a two-choice water reinforced fixed ratio (FR) 20 drug discrimination paradigm. In substitution tests, heroin (0.0625-0.5 mg/kg) and...