The effects of age on the binding parameters of 3H-SCH 23390, the most selective D-1 dopamine receptor ligand available at present, were studied in membrane preparations from rat striatum. When compared with 3 month old animals, there was a significant decrease in the density of 3H-SCH 23390 binding sites in 20 month old (-37%) and in 26 month old (-44%) rats, without alterations in the apparent dissociation constant values. No significant changes in the density or affinity of D-1 DA receptors were observed in 14 month old rats. In view of the behavioural effects mediated by D-1 DA receptors recently described (i.e., grooming, stereotypies and EEG desynchronization), the decrease in the density of these receptors in senescent rats may underlie some of the age-related alterations in dopaminergic functions in the rat brain.

Aging↗

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Failure of dark adaptation to upregulate D-1 dopamine receptors in retina of senescent rats.

The effect of aging on the binding parameters of 3H-SCH 23390, the most selective ligand of D-1 DA receptors, was studied in membrane preparations from the rat retina. DA-stimulated adenylate cyclase activity was also measured in order to better characterize the changes in retinal D-1 DA receptors induced by aging. The binding studies revealed that the density of 3H-SCH 23390 was increased (34 and 73%) in the retina of 14- and 26-month-old rats, when compared to young adult animals, respectively. In contrast, aging failed to alter the sensitivity of the adenylate cyclase to the action of DA. In fact, DA (10(-6) M to 10(-4) M) elicited a similar enhancement in cyclic AMP formation in retinal homogenates of both adult and senescent rats. Since dark adaptation increases the density of D-1 DA receptors in the retina of adult rats we studied the effect of light deprivation on 3H-SCH 23390 binding and DA-sensitive adenylate cyclase activity in the retina of senescent rats. As previously shown (25) light deprivation increased 3H-SCH 23390 binding and enhanced DA-sensitive adenylate cyclase activity in the retina of young adult rats. On the contrary, dark adaptation failed to increase 3H-SCH 23390 binding and to enhance DA-sensitive adenylate cyclase activity in the retina of senescent rats. Taken together these results indicate that D-1 DA receptors in the retina of aged rats have biochemical and functional properties different from those found in the retina of adult animals; these changes may result in an altered response to the physiological stimuli elicited by environmental lighting.

Adenylyl Cyclases↗

PubMedDate not supplied

Enhancement of GABA-dependent chloride channel by "in vivo" administration of ethanol.

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Animals↗

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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↗

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[Role of tryptophan in the physiological regulation of brain serotonin synthesis (author's transl)].

Tryptophan hydroilase in brain, normally is not saturated by its substrate; therefore the rate of tryptophan hydroxilation in brain is controlled by the concentration of tryptophan. In the other hand, brain tryptophan content is controlled by the ratio of the concentration of free tryptophan (i.e. not bound to serum proteins) to that of the other circulating amino acids, wich compete for the same transport mechanism from blood to brain. The administration of an amino acid mixture, containing all essential amino acids but not tryptophan, caused a parallel depletion of total and free serum tryptophan and of tryptophan and serotonin in brain. The mechanism of the observed fall in serum tryptophan is a rapid removed of endogenous tryptophan from circulation, secondary to an increased incorporation of tryptophan into proteins by the liver. These results suggest the hypothesis that brain serotonin synthesis is controlled by a perpherical mechanism.

Amino Acids↗

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Paradoxical reactions elicited by diazepam in children with classic autism.

Administration of diazepam (10 mg i.m.) to seven children (two girls and five boys) affected by infantile autism elicited paradoxical behavioural responses. Mainly, anxiogenic effect, unsocialized aggressive behaviour and explosive aggression were dramatically increased in comparison with the same symptoms present before and after treatment. The results show for the first time that benzodiazepines may elicit paradoxical behavioural response in autistic children. The possible involvement of an altered function at the level of GABA/benzodiazepine receptor complex is discussed.

Aggression↗

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