1,721,041 research outputs found
Effect of D-Ala2-morphiceptin on brain opiate receptors and aminergic systems during ontogenesis
No full textSerotonergic modulation of cortical rat noradrenergic system in the mechanism of action of antidepressant drugs
No full text[No abstract available
TEMPORAL SEQUENCE OF CHANGES IN CENTRAL NORADRENERGIC SYSTEM OF RAT AFTER PROLONGED ANTI-DEPRESSANT TREATMENT - RECEPTOR DESENSITIZATION AND NEUROTRANSMITTER INTERACTIONS
No full textIt has been shown that different receptor components may be involved in the adaptive changes occurring in noradrenergic (NE) neurones after prolonged periods of exposure to antidepressant drugs. In this report the desensitization of NE-coupled adenylate cyclase (NE-AC), β-adrenergic receptors and [3H]imipramine ([3H]-IMI or [3H]desipramine ([3H]DMI) binding sites have been temporally correlated with in vivo changes of NE utilization. Normetanephrine (NMN) was measured as indicator of NE synaptic events involved in antidepressant action. Concentrations of normetanephrine were increased after acute desipramine (DMI), viloxazine and mianserin administration. Following 3 days of treatment, the antidepressant-induced increase of normetanephrine became tolerant and NE neurones were resistant to the antidepressant effect until the 15th day of treatment. After two weeks, DMI elicited a significant decrease in the content of normetanephrine. A different pattern of changes has been found in the temporal modification of [3H]IMI recognition sites, β-adrenoceptors and NE-AC activity after chronic DMI treatment. Binding sites and receptors were down regulated after 10 days of treatment preceding the decrease in normetanephrine content. No down-regulation was observed in [3H]-DMI binding sites. Studies on the effects of antidepressants during brain maturation revealed that the mechanisms which cause desensitization of β-receptors and [3H]-IMI binding sites appear in the early stages of postnatal life. Since [3H]-IMI and [3H]-DMI recognition sites have been shown to be located on serotonergic (5-HT) and noradrenergic neurones respectively, the interactions between NE and 5-HT neurones could represent possible mechanisms implicated in receptor desensitization. The experiments presented involving lesions of 5-HT neurones have clearly demonstrated that NE release in rat cerebral cortex is under a tonic serotonergic influence. Alterations in the chemico-physical properties of the synaptic membranes might be also taken in consideration for the mechanisms underlying receptor modulation. In fact, evidence is provided that in neural tissue phospholipid methylation can be affected. In conclusion, the temporal sequence of changes in cortical noradrenergic neurones, after chronic antidepressant treatment, has demonstrated that integrated mechanisms are operative for the function of the overall system
Ontogenetic studies on mu, delta and kappa opioid receptors in rat brain
No full textThe ontogenetic pattern of multiple opioid binding sites in rat brain from birth until weaning has been investigated. [3H]-dihydromorphine ([3H]-DHM)3 [3H]-D-Ala2-D-Leu5-enkephalin ([3H]-DADLE) and [3H]-dynorphin A (1-8) ([3H]-DYN) as markers of mu (mu), delta (delta) and Kappa (kappa) sites were utilized respectively. The analysis of the kinetic parameters of [3H]-DHM binding shows that, at birth, mu sites possess an affinity similar to that of adult animals, and a density of 50%, which reaches 80% of the adult value at day 4. On the contrary, [3H]-DADLE binding in the first post-natal days shows low affinity and low density and delta-sites do not reach values comparable to the adult ones until the second week of life. The kinetic parameters of [3H]-DYN binding are almost undetectable during the preweanling period, due to the very low density of kappa sites at this stage of life. Displacement studies with mu-, delta- and kappa-selective ligands show that the Ki values on [3H]-DHM binding sites were similar in 4 day old and adult animals for all the tested compounds, whereas Ki values on [3H]-DADLE and [3H]-DYN binding sites reflected an immaturity of delta and kappa receptors. In conclusion, our data suggest that multiple opioid receptors follow different ontogenetic patterns. In the first stages of life only mu receptors are almost mature and possibly mediate endogenous opioid actions and exogenous opiate pharmaco-toxicological effects
CAMP BINDING-PROTEINS IN THE RAT CEREBRAL-CORTEX AFTER ADMINISTRATION OF SELECTIVE 5-HT AND NE REUPTAKE BLOCKERS WITH ANTIDEPRESSANT ACTIVITY
No full textThis study was undertaken to evaluate the cyclic adenosine monophosphate (cAMP) binding proteins in the cerebral cortex of rat after short- and long-term administration with antidepressants. Prolonged treatment with different antidepressants that inhibit serotonin or norepinephrine uptake such as fluoxetine and the (+) enantiomer of oxaprotiline, respectively, was able to induce an increase in the photoactivated incorporation of 8-N3-[P-32]cAMP into a protein band with apparent molecular weight of 52,000 in both soluble and crude microtubule fraction. On the contrary, chronic treatment with the (-) enantiomer of oxaprotiline, which does not affect monoamine uptake, failed to produce this effect. Moreover, no changes were observed after acute or in vitro addition of antidepressants, suggesting that modification in the cAMP binding may be related to adaptive changes elicited by prolonged antidepressants treatment. In conclusion, our studies indicate that the cAMP binding protein associated with the crude microtubule fraction could be an intracellular target for the action of antidepressant drugs
Age-related changes in 5HT uptake and [3H]imipramine binding sites in rat cerebral cortex
No full text
METABOTROPIC GLUTAMATE RECEPTORS NEGATIVELY COUPLED TO ADENYLATE CYCLASE INHIBIT N-METHYL-D-ASPARTATE RECEPTOR ACTIVITY AND PREVENT NEUROTOXICITY IN MESENCEPHALIC NEURONS IN VITRO
No full textThe functional effects of G protein-linked glutamate receptor activation have been studied in mouse mesencephalic neurons in vitro. We have been able to identify two receptor classes, one linked to phosphoinositide hydrolysis and another that inhibits adenylate cyclase. The agonist (1S,3R)-aminocyclo-pentane-1,3-dicarboxylate (ACPD) affected the two responses with similar potency (EC(50) = 2 and 7 mu M, respectively). In contrast, (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine selectively decreased adenylate cyclase activity (EC(50) = 150 nM), without interfering with the phosphoinositide pathway. Activation of ion channel-linked glutamate receptors in mesencephalic neurons leads to cGMP formation. In this study, we demonstrate that cell pretreatment with ACPD or (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine prevented, in a dose-dependent fashion, N-methyl-D-aspartate (NMDA)-induced cGMP formation but not the kainate-stimulated response. The pharmacological profile suggests that receptors that are negatively coupled to adenylate cyclase are responsible for this effect. Coexposure of neurons to ACPD and Ba2+, a K+ channel blocker, counteracted the ACPD-induced blockade of NMDA receptors, suggesting that activation of K+ conductances could be involved in the post-transduction events triggered by metabotropic receptors in the mesencephalon. Neuronal treatment with NMDA for 10 min caused a reduction in mitochondrial activity. Direct inhibition of nitric oxide synthase with the inhibitor N-G-nitro-L-arginine or removal of extracellular nitric oxide with reduced hemoglobin did not prevent this metabolic impairment, thus excluding a role for nitric oxide in this test for excitotoxicity. On the contrary, the mitochondrial function was maintained when neurons exposed to NMDA were preincubated with metabotropic receptor agonists. To summarize, our results suggest that metabotropic receptors that are negatively coupled to adenylate cyclase exert modulatory control specifically on NMDA receptor activity. This event could also contribute to the reduction of neurotoxic effects due to NMDA receptor hyperactivity
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