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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.
J Psychopharmacol. 2012 Apr; 26(4):525-31.JP

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.

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Authors+Show Affiliations

Roncon CM
Department of Pharmacology and Therapeutic, State University of Maringá, Maringá, Brazil.
Biesdorf C
No affiliation info available
Santana RG
No affiliation info available
Zangrossi H
No affiliation info available
Graeff FG
No affiliation info available
Audi EA
No affiliation info available

MeSH

AnimalsAntidepressive Agents, Second-GenerationFluoxetineMaleMaze LearningMotor ActivityNaloxoneOpioid PeptidesPanic DisorderPeriaqueductal GrayRatsRats, WistarSerotonin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22279131

Citation

Roncon, Camila M., et al. "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." Journal of Psychopharmacology (Oxford, England), vol. 26, no. 4, 2012, pp. 525-31.
Roncon CM, Biesdorf C, Santana RG, et al. 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. J Psychopharmacol. 2012;26(4):525-31.
Roncon, C. M., Biesdorf, C., Santana, R. G., Zangrossi, H., Graeff, F. G., & Audi, E. A. (2012). 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. Journal of Psychopharmacology (Oxford, England), 26(4), 525-31. https://doi.org/10.1177/0269881111434619
Roncon CM, et al. 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. J Psychopharmacol. 2012;26(4):525-31. PubMed PMID: 22279131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Roncon,Camila M, AU - Biesdorf,Carla, AU - Santana,Rosangela G, AU - Zangrossi,Hélio,Jr AU - Graeff,Frederico G, AU - Audi,Elisabeth A, Y1 - 2012/01/24/ PY - 2012/1/27/entrez PY - 2012/1/27/pubmed PY - 2012/8/18/medline SP - 525 EP - 31 JF - Journal of psychopharmacology (Oxford, England) JO - J Psychopharmacol VL - 26 IS - 4 N2 - 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. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/22279131/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_ L2 - https://journals.sagepub.com/doi/10.1177/0269881111434619?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -