title: 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.
abstract: 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 μg/0.5 μL) 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 μg/0.5 μL). 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.
authors.affiliation: Department of Pharmacology and Therapeutic, State University of Maringá, Maringá, Brazil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Roncon
authors.forename: Carla
authors.initials: C
authors.lastname: Biesdorf
authors.forename: Rosangela G
authors.initials: RG
authors.lastname: Santana
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
authors.forename: Frederico G
authors.initials: FG
authors.lastname: Graeff
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Audi
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D018847:Opioid Peptides / Q000502:physiology*; D016584:Panic Disorder / Q000188:drug therapy*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D018847:Opioid Peptides; D005473:Fluoxetine; D012701:Serotonin; D009270:Naloxone