RESUMO
Previous work has shown that intraperitoneal administration of riparin III (ripIII) reduces immobility time in the forced swimming test (FST), which suggests potential antidepressant activity. As the mechanism of action is not completely understood, this study is aimed at investigating the antidepressant-like action of ripIII. Following intraperitoneal administration of ripIII at doses of 25 and 50 mg/kg, there were decreases in the immobility time in the FST and tail suspension test without accompanying changes in ambulation (data not shown). The pretreatment of mice with sulpiride (50 mg/kg, i.p.), prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and p-chlorophenylalanine (PCPA, 100 mg/kg, i.p. for, four consecutive days) significantly prevented the anti-immobility effect of ripIII in the FST. On the other hand, the anti-immobility effect of ripIII (50 mg/kg, v.o.) was not altered by pretreatment of mice with SCH23390 (15 µg/kg, i.p.) Furthermore, ripIII potentiated the sleeping latency and sleeping time of the pentobarbital-induced sleeping time test and also potentiated apomorphine (16 mg/kg, i.p.)-induced hypothermia in mice. In conclusion, the present study provides evidence that the antidepressant-like effect of ripIII is dependent on its interaction with the serotonergic, noradrenergic (α1- and α2- receptors), and dopaminergic (dopamine D2 receptors) systems.
Assuntos
Antidepressivos/uso terapêutico , Benzamidas/uso terapêutico , Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Neurônios/efeitos dos fármacos , Tiramina/análogos & derivados , Administração Oral , Agonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Animais , Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Benzamidas/administração & dosagem , Encéfalo/metabolismo , Brasil , Depressão/metabolismo , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/uso terapêutico , Etnofarmacologia , Frutas/química , Frutas/crescimento & desenvolvimento , Guiana , Lauraceae/química , Lauraceae/crescimento & desenvolvimento , Masculino , Camundongos , Neurônios/metabolismo , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D2/metabolismo , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/uso terapêutico , Tiramina/administração & dosagem , Tiramina/uso terapêuticoRESUMO
Local administration of ascorbic acid (Asc) at a supraphysiological concentration inhibits the cutaneous vasoconstrictor response to local cooling (LC). However, whether orally ingesting Asc inhibits the LC-induced vasoconstrictor response remains unknown. The purpose of the present study was to examine the acute influence of oral Asc on the adrenergic vasoconstrictor response to LC in human skin. In experiment 1, skin blood flow (SkBF) was measured by laser-Doppler flowmetry at three sites (forearm, calf, palm). The three skin sites were locally cooled from 34 to 24°C at -1°C/min and maintained at 24°C for 20 min before (Pre) and 1.5 h after (Post) oral Asc (2-g single dose) or placebo supplementation. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before LC. Oral Asc enhanced (P < 0.05) the reductions in CVC in the forearm (Pre, -50.3 ± 3.3%; Post, -57.8 ± 2.2%), calf (Pre, -52.6 ± 3.7%; Post, -66.1 ± 4.3%), and palm (Pre, -46.2 ± 6.2%; Post, -60.4 ± 5.6%) during LC. The placebo did not change the responses at any site. In experiment 2, to examine whether the increased vasoconstrictor response caused by oral Asc is due to the adrenergic system, the release of neurotransmitters from adrenergic nerves in forearm skin was blocked locally by iontophoresis of bretylium tosylate (BT). Oral Asc enhanced (P < 0.05) the reductions in CVC at untreated control sites but did not change the responses at BT-treated sites during LC. In experiment 3, to further examine whether adrenergically mediated vasoconstriction is enhanced by oral Asc, 0.1 mM tyramine was administered using intradermal microdialysis in the forearm skin at 34°C in the Pre and Post periods. Oral Asc increased (P < 0.05) the tyramine-induced reduction in CVC. These findings suggest that oral Asc acutely enhances the cutaneous vasoconstrictor responses to LC through the modification of adrenergic sympathetic mechanisms.
Assuntos
Fibras Adrenérgicas/efeitos dos fármacos , Ácido Ascórbico/administração & dosagem , Vasos Sanguíneos/inervação , Hipotermia Induzida , Temperatura Cutânea , Pele/irrigação sanguínea , Vasoconstrição/efeitos dos fármacos , Administração Cutânea , Administração Oral , Fibras Adrenérgicas/metabolismo , Análise de Variância , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Tosilato de Bretílio/administração & dosagem , Feminino , Humanos , Iontoforese , Japão , Fluxometria por Laser-Doppler , Masculino , Microdiálise , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fatores de Tempo , Tiramina/administração & dosagem , Adulto JovemRESUMO
The effects of alpha-linolenic acid diet deficiency on rat dopaminergic metabolism were investigated in the frontal cortex of male 2-3 month-old rats using the microdialysis method. Increased basal levels of dopamine metabolites were observed in the frontal cortex of awake deficient rats, without modification of dopamine levels. Moreover, using KCl perfusion which releases newly synthesized dopamine, no difference was observed in anaesthetized deficient rats versus control rats. In addition, a decrease in dopamine release was observed in anaesthetized deficient rats versus control rats after tyramine stimulation, which is known to induce release of dopamine from vesicular stores. A working model is proposed which suggests that a chronic n-3 polyunsaturated fatty acids (PUFA) deficiency may lead to modifications in the internalization of dopamine in the storage pool in the frontal cortex.
Assuntos
Dieta com Restrição de Gorduras/efeitos adversos , Gorduras Insaturadas na Dieta/administração & dosagem , Dopamina/metabolismo , Lobo Frontal/metabolismo , Ácido alfa-Linolênico/deficiência , Análise de Variância , Animais , Feminino , Lobo Frontal/efeitos dos fármacos , Masculino , Microdiálise/métodos , Perfusão , Ratos , Ratos Wistar , Técnicas Estereotáxicas , Transmissão Sináptica/efeitos dos fármacos , Tiramina/administração & dosagem , Ácido alfa-Linolênico/administração & dosagemRESUMO
We made stereotaxic microinjections of adrenoceptor agonists and the catecholamine-releasing agent, tyramine, into the preoptic anterior hypothalamic area (PO/AHA) or the medial basal hypothalamus (MBH) of unstressed rats. Growth hormone (GH) plasma concentrations were measured serially before and after intrahypothalamic injections. Noradrenaline and phenylephrine inhibited GH secretion wherever injected but were effective at lower doses in the PO/AHA. Clonidine stimulated GH secretion at both sites, at several doses in the MBH and only at one dose in the PO/AHA. Tyramine inhibited GH when injected in the PO/AHA, but not in the MBH. We conclude: (a) alpha 1 inhibition is predominant over alpha 2 stimulation of GH on or near somatostatin neurons; (b) alpha 2 stimulation predominates over alpha 1 inhibition of GH on or near GRF neurons, and (c) endogenous catecholamines in the PO/AHA have a predominantly inhibitory effect on GH secretion.