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A Concas

Publications and source records attributed to A Concas.

80 records · Page 5Linked to original sources

Age-related changes of benzodiazepine and GABA binding sites in the rat retina.

The changes in the number and sensitivity of benzodiazepine and GABA binding sites in the rat retina during postnatal development, adulthood and ageing and their functional relationship at different ages have been studied. Data indicate an increase in the total number of both GABA and benzodiazepine binding sites with age. In contrast, the activation of retinal benzodiazepine receptor binding by GABA is significantly reduced in aged rats with respect to young adult and newborn rats. Moreover, the activation of retinal benzodiazepine receptor binding induced by dark exposure of the animals is present in young adult rats but is lost in aged rats. These results suggest that in the retina of aged rats there is an increase of GABA and benzodiazepine receptors which have lost their functional connection.

Aging↗

Rapid changes in GABA binding induced by stress in different areas of the rat brain.

Rats habituated to handling preceding sacrifice have higher [3H]GABA receptor binding in different brain areas (cerebellum, frontal cortex, caudate nucleus) than naive animals. The increase in GABA binding in handling-habituated rats is due to an increase in the number of receptors (Bmax) with no changes in the affinity of GABA binding for its ligand (Kd). Foot shock causes a sudden fall in GABA binding in handling-habituated rats but does not, or only slightly, in naive ones. The results indicate that stress causes a rapid decrease in GABA receptor binding in the central system and that the GABA binding values which are usually considered as normal are, in fact, values decreased by the handling manoeuvers preceding sacrifice.

Animals↗

Methyl mercury enhances [3H]diazepam binding in different areas of the rat brain.

Three days after the acute oral administration of methyl mercury (MeHg), a 27-60% increase in the total number of binding sites for [3H]diazepam was seen in the retina and different areas of the rat brain, with no change, except in the retina, in the apparent dissociation constant for its ligand. In contrast, MeHg failed to change [3H]spiroperidol and [3H]GABA binding in the same areas. Moreover, MeHg decreased cyclic GMP content in the cerebellar cortex. The various possible mechanisms involved in the action of MeHg on benzodiazepine binding are discussed.

Animals↗

Denervation supersensitivity for benzodiazepine receptors in the rat substantia nigra.

The injection of kainic acid into the substantia nigra causes, 3 weeks after treatment, a 40% decrease in the total number of binding sites for [3H]diazepam with an increase in the dissociation constant. This decrease was restored to approximately normal by the subsequent injection of kainic acid into the striatum, homolateral to the lesioned substantia nigra. The injection of kainic acid into the striatum of intact animals failed to modify the number of [3H]diazepam binding sites but increased the KD. The results indicate that benzodiazepine binding sites in the substantia nigra are partly located on kainic acid sensitive elements (probably interneurons) and, partly, on kainic acid resistant ones. These binding sites become supersensitive after degeneration of striato-nigral pathways. The possible role of GABAergic denervation of the substantia nigra in the development of benzodiazepine binding sites supersensitivity is discussed.

Animals↗

Kainic acid-induced lesion of rat retina: differential effect on cyclic GMP and benzodiazepine and GABA receptors.

Intraocular injection of kainic acid caused a marked decrease in GABA content in the rat retina and the almost complete loss of GAD activity in this tissue, within 3 days. Moreover, kainic acid produced a decrease of approximately 65% in the number of both [3H]diazepam and [3H]GABA binding sites without changing the apparent dissociation constants for their ligands. In contrast to that in brain areas, cyclic GMP content in the retina is neither influenced by kainic acid nor by the systemic administration of diazepam and muscimol.

Animals↗

Stress and neurosteroids in adult and aged rats.

The progesterone derivative 3 alpha-hydroxy-5 alpha-pregnan-20 one (allopregnanolone/AP) and the deoxycorticosterone derivative 3 alpha-21-dihydroxy-5 alpha- pregnan-20 one (allotetra-hydrodeoxycorticosterone/THDOC) are endogenous neuroactive steroids endowed with neuromodulatory actions in the central nervous system. Their best-characterized membrane-receptor-dependent action consists in the amplification of GABA-gated chloride currents mediated by specific interactions with the GABAA receptor complex, which appears responsible for the pharmacological effects (anxiolytic, anticonvulsant, hypnotic/anaesthetic) of exogenously administered AP and THDOC. Several acute stress paradigms and different negative allosteric modulators (isoniazid and FG 7142) of GABAA receptors time dependently increase brain and plasma concentrations of AP and THDOC only in intact or sham-operated but not in adrenalectomized-orchiectomized rats. These results suggest that acute stress and inhibitors of GABAA receptors increase the brain and plasma neurosteroid concentrations via a reduction of the inhibitory action exerted by GABA on the hypothalamic-pituitary-adrenal axis. The comparison between the time course of the changes in GABAA receptor function and of their behavioral correlates (proconflict behavior) and that of the changes of endogenous neuroactive steroids are consistent with the view that AP and THDOC may play a role in restoring the GABAergic tone to prestress conditions, by limiting the duration and the extent of its stress-induced reduction. The acute stress-elicited increase of AP and THDOC is observed in adult as well as in aged rats, which show a reduced basal GABAergic transmission and a greater response to the effect of stress in terms of their brain cortical neuroactive steroid concentrations than adult rats.

Aging↗