The panicolytic-like effect of fluoxetine in the elevated T-maze is mediated by serotonin-induced activation of endogenous opioids in the dorsal periaqueductal grey
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
15/10/2013
15/10/2013
2012
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Resumo |
Serotonin (5-HT), opioids and the dorsal periaqueductal grey (DPAG) have been implicated in the pathophysiology of panic disorder. In order to study 5-HT-opioid interaction, the opioid antagonist naloxone was injected either systemically (1 mg/kg, i.p.) or intra-DPAG (0.2 mu g/0.5 mu L) to assess its interference with the effect of chronic fluoxetine (10 mg/kg, i.p., daily for 21 days) or of intra-DPAG 5-HT (8 mu g/0.5 mu L). Drug effects were measured in the one-escape task of the rat elevated T-maze, an animal model of panic. Pretreatment with systemic naloxone antagonized the lengthening of escape latency caused by chronic fluoxetine, considered a panicolytic-like effect that parallels the drug's therapeutic response in the clinics. Pretreatment with naloxone injected intra-DPAG antagonized both the panicolytic effect of chronic fluoxetine as well as that of 5-HT injected intra-DPAG. Neither the performance of the inhibitory avoidance task in the elevated T-maze, a model of generalized anxiety nor locomotion measured in a circular arena was affected by the above drug treatments. These results indicate that the panicolytic effect of fluoxetine is mediated by endogenous opioids that are activated by 5-HT in the DPAG. They also allow reconciliation between the serotonergic and opioidergic hypotheses of panic disorder pathophysiology. CAPES CNPq Fundacao de Amparo ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas de Ribeirao Preto (FAEPA) |
Identificador |
JOURNAL OF PSYCHOPHARMACOLOGY, LONDON, v. 26, n. 4, pp. 525-531, APR, 2012 0269-8811 http://www.producao.usp.br/handle/BDPI/35125 10.1177/0269881111434619 |
Idioma(s) |
eng |
Publicador |
SAGE PUBLICATIONS LTD LONDON |
Relação |
JOURNAL OF PSYCHOPHARMACOLOGY |
Direitos |
restrictedAccess Copyright SAGE PUBLICATIONS LTD |
Palavras-Chave | #SEROTONIN #ENDOGENOUS OPIOIDS #ANTIDEPRESSANT #PANIC #ANIMAL MODEL #PERIAQUEDUCTAL GREY #PANIC DISORDER #NUCLEUS-ACCUMBENS #ANIMAL-MODELS #ANXIETY #GRAY #MORPHINE #LACTATE #ANTIDEPRESSANTS #RESPONSES #NALOXONE #CLINICAL NEUROLOGY #NEUROSCIENCES #PHARMACOLOGY & PHARMACY #PSYCHIATRY |
Tipo |
article original article publishedVersion |