GABAergic Inhibitory System Research Articles

Neurochemistry of GABAergic system in cerebral cortex chronically exposed to bromide in vivo.

Neurochemical correlates of GABAergic synaptic transmission [binding, uptake, metabolism, and tissue content of gamma-aminobutyric acid (GABA)] were investigated in the cortex of rats that had been given 27 mM bromide in drinking water for periods of time ranging from 1 day to 1 month. No effect of bromide on any of the parameters was found and it is concluded that chronic administration of bromide has no profound effect on GABAergic inhibitory system in the rat cortex.

Prophylaxis of amygdala kindling-induced epileptogenesis: Comparison of a GABA uptake inhibitor and diazepam

The prophylactic effect of an inhibitor of synaptosomal GABA uptake, SK&F 89976-A (N-[4,4-diphenyl-3-butenyl]-nipecotic acid), on the development of amygdala kindled seizures was studied in adult female rats. For comparative purposes, the action of diazepam was also investigated. Dosages of SK&F 89976-A and diazepam which were previously shown to be the ED50 for seizure inhibition in fully kindled rats (15 mg/kg and 2 mg/kg i.p., respectively) were administered daily 30 min prior to amygdala stimulation in naive, unkindled rats. Both drugs inhibited the evolution of full kindled seizure activity and markedly suppressed kindling-associated increases in the duration of behavioral and electrographic seizures. Control rats developed fully kindled stage 5 seizures after 8.9 +/- 1.1 amygdala stimulations but drug-treated rats did not progress beyond an early stage of kindled seizures as long as the animals were treated with the drugs (22 days). Diazepam produced significant CNS depressant effects throughout the course of administration but SK&F 89976-A prevented kindling with no depressant side effects. The ability of SK&F 89976-A and diazepam to inhibit the development of full amygdala kindled seizures may be related to enhancement of central inhibitory GABAergic systems.

Mechanisms contributing to sparing of function following neonatal damage to spinal pathways.

When spinal pathways are damaged in newborn animals and their behavior is examined in adulthood, motor function is superior to that seen in animals in which the same lesion was made in adulthood. This is the infant lesion effect. After neonatal sensorimotor cortex ablation, spinal hemisection, or spinal transection, sparing of contact placing is observed; in adults, all three lesions abolish contact placing permanently. The anatomical correlates of the infant lesion effect are different in each case. After neonatal unilateral cortical ablation, an exuberant crossed corticorubral pathway from the other cortex fails to retract (as it does normally), giving the remaining cortex a path for mediating contact placing. After neonatal spinal hemisection, late-developing corticospinal axons take an aberrant course around the lesion and mediate contact placing. After neonatal transection, the spinal inhibitory GABA-ergic system fails to develop to a normal extent. This may result in abnormal enhancement of spinal reflex pathways, especially since some dorsal roots increase their input after that lesion. Thus, a number of factors may influence the outcome of damage to the developing nervous system.

Type A and B gaba receptors mediate inhibition of acetylcholine release from cholinergic nerve terminals in the superior cervical ganglion of rat

The effects of ?-amino-n-butyric acid (GABA), (+)bicuculline, isoguvacine and 3-(4-chlorophenyl)-4-aminobutyrate [(+/-)baclofen] on the K-induced release of [(3)H]acetylcholine (ACh) were studied in the superior cervical ganglia of the rat in vitro. GABA and isoguvacine inhibited [(3)H]ACh release and these inhibitions were reversible by (+)bicuculline. Furthermore, the release of [(3)H]ACh was also inhibited by (+/-)baclofen. In receptor-binding studies, binding of [(3)H]GABA to membrane preparations from the superior cervical ganglia was inhibited by both (+/-)baclofen and (+)bicuculline. It is concluded that the inhibitory effect of GABA on the release of ACh can be mediated by GABA(A)(bicuculline-sensitive) and by GABA(B) (baclofen-activated) receptors. Our findings are compatible with the existence of a non-synaptic GABAergic inhibitory system involving GABA(A) and GABA(B) receptors on cholinergic nerve terminals in the superior cervical ganglion of rat.

State of peripheral catecholaminergic systems during pharmacologic correction of immobilization stress by sodium hydroxybutyrate

Investigations have shown that administration of sodium hydroxybutyrate (the sodium salt of y-hydroxybutyric acid -GHBA) to stressed animals reduces activation of the pituitarysympathicoadrenal system and limits the development of stress-induced lesions in various internal organs [6, 14]. In the existing view, the antistressor effect of this compound is exerted at the level of higher autonomic centers of the brain, and consists of activation of the inhibitory GABA-ergic system; this, in turn, prevents excessive excitation of the stress-realizing systems of the body, including the catecholaminergic system [2, 8].

Down regulation of striatal dopamine receptors in experimental hepatic encephalopathy

Dopamine receptors were studied in striatal synaptosomes prepared from rat brain with hepatic encephalopathy induced by galactosamine-HCl and documented by visual evoked potential recordings. In order to further characterize the model, plasma amino acid levels and striatal catecholamines and octopamine levels were assayed. In agreement with previous reports in animal and in man, plasma amino acids were increased both in mild and severe stage of this pathology. Striatal levels of norepinephrine and dopamine fell during the development of coma while octopamine rose. Dopamine binding studies showed a decrease in the affinity during the mild stage and a reduction of receptor numbers in the severe stage of encephalopathy. The overall results, in the light of previous reports on GABA receptor studies, seem to indicate the presence in the development of encephalopathy of an imbalance between the dopaminergic and the GABAergic system leading to a prevalence of GABAergic inhibitory system.

The ventromedullary hypotensive effect of muscimol in the anaesthetized cat.

Muscimol, a rigid analogue of GABA, was injected into the CNS of urethane-anaesthetized, normotensive cats. Bilateral microinjections of a small dose of muscimol (100 ng/kg, 0.5 microliter on each side) in the nucleus reticularis lateralis (NRL) induced hypotension. The marked fall in blood pressure obtained by injecting 1 microgram/kg of muscimol unilaterally into the NRL is completely reversed by subsequent local administration of bicuculline (5 microgram/kg, 0.5 microliter), a specific GABA antagonist. These data confirm that a GABAergic inhibitory system modulates the pressor tonic structures localized in the region of the NRL and that the anteroventral part of the medulla oblongata includes a trigger zone for the hypotensive action of muscimol.

Disturbances of metabolism and cardiac function under the action of emotional painful stress and their prophylaxis.

Under the action of severe emotional painful stress the high concentration of catecholamines leads to the activation of peroxide oxidation of lipids in myocardium. Lipid peroxides affect membranes, responsible for the transport of calcium. As a result local necrobiosis and disturbances of the contractile function of the heart are developed. This emotional painful stress is regularly followed by activation of the inhibitory GABA-ergic system of the animal brains, which restricts the intensity and the time of stress syndromes. The injection of one of the metabolites of GABA-ergic system - gamoxibutirate (GOBA) - prior to stress essentially decreases the intensity of stress syndrome and prevents the stress affection of the heart muscle.

Alleviation of stress and gastric ulceration by gamma-hydroxybutyric acid

The effect of preliminary administration of sodium hydroxybutyrate (GHBA) on activation of the adrenergic and pituitary-adrenal systems during emotional-pain stress and on the severity of gastric ulcers after the end of such stress was studied in experiments on rats. Preliminary administration of GHBA was shown to restrict excitation of the systems responsible for stress and to prevent the development of ulceration of the gastric mucosa. It can be suggested that activation of the GABA-ergic inhibitory system arising during stress is the sole mechanism of limitation of the stress reaction and of prevention of stress-induced injuries.