1,721,053 research outputs found
Much excitement about antidepressants, DBI and c-FOS
No full textThis article briefly outlines the background and major findings of the research projects in which, together
with a number of skilled and enthusiastic collaborators, I was involved at FGIN under the mentorship
of the late Dr. Erminio Costa.The topics covered are (ì) our search for an endogenous ligand of the [3H]-
imipramine binding site, as an approach to shed light on the still today elusive mechanisms underlying
the therapeutic action of antidepressant drugs; (ìì) our attempt to correlate psychopathological states,
characterized by dysfunctions of the GABAergic neurotransmission, with an altered brain content of
Diazepam binding inhibitor (DBI), a peptide that exerts a direct negative modulation of GABAA receptor
function and also, by binding to the mitochondrial benzodiazepine receptor, increases the brain content of
GABAA receptor-active neurosteroids; (ììì) our demonstration that the activation of the glutamate/NMDA
receptor, throughstimulation of several intracellular signaling pathways, induces the expression of the
early inducible gene c-fos, a mechanism proposed to underlie glutamate-mediated neuronal plasticity
Approcci metodologici per una farmacoterapia moderna: Evidence Based Medicine e Systems Medicine
No full textStress and neurosteroids in adult and aged rats
No full textThe 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
Neurosteroids modulate GABA(A) receptor structure and function during pregnancy and delivery in the rat brain.
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Activation of specific glutamate receptor subtypes increases C-fos proto-oncogene expression in primary cultures of neonatal rat cerebellar granule cells
No full textIn primary cultures of rat cerebellar granule cells the activation of excitatory amino acid receptors by 1-glutamate enhances the steady state level of c-fos proto-oncogene messenger RNA. This effect is blocked by magnesium (1mM) as well as by the glutamate receptor antagonist 2-amino-5-phosphono-valerate (APV). Among the other excitatory amino acid agonists N-methyl-D-Aspartate (NMDA) and quisqualate also increased c-fos mRNA content, the latter however to a significantly lesser extent, while kainate failed to modify the basal level of c-fos expression. The addition of the muscarinic agonist carbachol or of the inhibitory neurotransmitter GABA did not affect the basal level of c-fos mRNA. This data demonstrate for the first time that activation of signal transduction at a specific excitatory amino acid receptor subtype can increase the steady state level of c-fos proto-oncogene mRNA in primary culture of cerebellar neurons
Different effects of serotonin antagonists on 3H-mianserin and 3H-ketanserin recognition sites
No full textIn minces prepared from the frontal cortex of rats treated with ketanserin (10 mg/kg i.p.) or mianserin (5 mg/kg i.p.) twice daily for 21 days, the Vmax of the adenylate cyclase stimulated by NE (100 microM) is attenuated, suggesting that ketanserin and mianserin share with a number of antidepressants the ability to attenuate the adenylate cyclase stimulation by NE. Ketanserin, given with the above mentioned dose schedule for 7 consecutive days, reduced the Bmax of 5HT2 recognition sites but failed to change either the Bmax or the apparent Kd of H-mianserin binding. A significant decrease in the Bmax of 5HT2 binding sites is elicited also by a single injection of mianserin (1). This drug also down-regulates its own binding when given twice daily for 3 weeks. From this and other information (2,3), it is concluded that ketanserin and mianserin bind to distinct recognition sites. The possibility that 5HT2 and mianserin recognition sites are functionally related and that serotonergic synapses are modulated by multiple chemical signals might be considered
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