RESUMEN
Hypothalamic paraventricular nucleus (PVN) has an important role in the regulation of water and sodium intake. Several researches described the presence of 5-HT(1) receptors in the central nervous system. 5-HT(1A) was one of the prime receptors identified and it is found in the somatodendritic and post-synaptic forms. Therefore, the aim of this study was to investigate the participation of serotonergic 5-HT(1A) receptors in the PVN on the sodium intake induced by sodium depletion followed by 24 h of deprivation (injection of the diuretic furosemide plus 24 h of sodium-deficient diet). Rats (280-320 g) were submitted to the implant of cannulas bilaterally in the PVN. 5-HT injections (10 and 20 microg/0.2 microl) in the PVN reduced NaCl 1.8% intake. 8-OH-DPAT injections (2.5 and 5.0 microg/0.2 microl) in the PVN also reduced NaCl 1.8% intake. pMPPF bilateral injections (5-HT(1A) antagonist) previously to 8-OH-DPAT injections have completely blocked the inhibitory effect over NaCl 1.8% intake. 5-HT(1A) antagonists partially reduced the inhibitory effect of 5-HT on NaCl 1.8% intake induced by sodium depletion. In contrast, the intake of palatable solution (2% sucrose) under body fluid-replete conditions was not changed after bilateral PVN 8-OH-DPTA injections. The results show that 5-HT(1A) serotonergic mechanisms in the PVN modulate sodium intake induced by sodium loss. The finding that sucrose intake was not affected by PVN 5-HT(1A) activation suggests that the effects of the 5-HT(1A) treatments on the intake of NaCl are not due to mechanisms producing a nonspecific decrease of all ingestive behaviors.
Asunto(s)
Núcleo Hipotalámico Paraventricular/metabolismo , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Receptor de Serotonina 5-HT1A/metabolismo , Cloruro de Sodio Dietético/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralin/química , 8-Hidroxi-2-(di-n-propilamino)tetralin/metabolismo , Animales , Masculino , Núcleo Hipotalámico Paraventricular/química , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Agonistas de Receptores de Serotonina/química , Agonistas de Receptores de Serotonina/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
RATIONALE: Administration of 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptor agonists into the dorsal periaqueductal gray (DPAG) inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with the antipanic compound imipramine enhances the DPAG 5-HT1A- and 5-HT2A-receptor-mediated inhibition of escape, implicating these receptors in the mode of action of panicolytic drugs. OBJECTIVES: In the present study, we investigated whether the inhibitory effect on escape elicited by the intra-DPAG injection of 5-HT1A and 5-HT2A receptor agonists is also enhanced after treatment with fluoxetine, another widely used antipanic drug. The effects of fluoxetine were compared to those of buspirone, an anxiolytic drug without major effect on panic disorder. METHODS: Male Wistar rats, subchronically (3-6 days) or chronically (21-24 days) treated with fluoxetine (10 mg/kg i.p.) or chronically treated with buspirone (0.3 mg/kg i.p.), were intra-DPAG injected with 5-HT (20 nmol), the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 8 nmol) or the preferential 5-HT2A receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl) piperazine dihydrochloride (DOI; 16 nmol). The intensity of electrical current that applied to the DPAG-evoked escape behavior was measured before and after the microinjection of these agonists. RESULTS: The electrical current necessary to produce escape was increased after the microinjection of the three 5-HT receptor agonists in all groups of animals tested. However, this panicolytic-like effect was significantly higher in animals receiving long-term treatment with fluoxetine. CONCLUSIONS: The results suggest that facilitation of the 5-HT1A- and 5-HT2A-receptor-mediated inhibition of DPAG neuronal activity is implicated in the beneficial effect of antidepressants in panic disorder.
Asunto(s)
Ansiolíticos/farmacología , Buspirona/farmacología , Fluoxetina/farmacología , Sustancia Gris Periacueductal/fisiología , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Receptor de Serotonina 5-HT2A/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/metabolismo , Anfetaminas/administración & dosificación , Anfetaminas/farmacología , Animales , Ansiolíticos/administración & dosificación , Buspirona/administración & dosificación , Fluoxetina/administración & dosificación , Masculino , Microinyecciones , Ratas , Ratas Wistar , Serotonina/metabolismo , Agonistas de Receptores de Serotonina/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificaciónRESUMEN
The presence of serotonin 5-HT1A receptors and their physiological role were further characterized in the goldfish retina. The effects of the 5-HT6/7 receptor antagonists pimozide, fluphenazine and amoxapine, the 5-HT1A receptor antagonist WAY-100,135, and the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, on the 5-HT1A receptor agonist [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to retinal membranes, were evaluated. In addition, the effects of serotonin, 8-hydroxy-2-(di-n-propylamino)tetralin, WAY-100,135, the adenylate cyclase inhibitors SQ22536 and MDL12330A, and the cyclic AMP analog 8-bromoadenosine-3':5' cyclic monophosphate were also studied on neuritic outgrowth from retinal explants. WAY-100,135 but not 5-HT6/7 receptor antagonists inhibited [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to retinal membranes N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline decreased [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding sites up to 70%, while receptor turnover was similar to that reported in other tissues. Serotonin and 8-hydroxy-2-(di-n-propylamino)tetralin stimulated cyclic AMP production, both ex vivo and in vitro, and these increases were related to inhibition of neuritic outgrowth. The inhibitory effect was reduced by SQ22536 and by WAY-100,135, and was mimicked by 8-bromoadenosine-3':5'cyclic monophosphate. This study supports previous findings about the role of serotonin as a regulator of axonal outgrowth during in vitro regeneration of the goldfish retina and demonstrates that this effect is mediated, at least in part, by 5-HT1A receptors through a mechanism which involves an increase of cyclic AMP levels.