Roger L H Pobbe1, Hélio Zangrossi. 1. Department of Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, Brazil.
Abstract
RATIONALE: It has been proposed that the serotonergic pathway that connects the dorsal raphe nucleus (DRN) to the dorsal periaqueductal gray (DPAG) is implicated in the regulation of escape, a behavior that has been related to panic. OBJECTIVES: We further evaluated this hypothesis by investigating whether intra-DRN injection of the 5-HT(1A) receptor antagonist WAY-100635 changes the escape response of rats submitted to the elevated T-maze. This test also measures inhibitory avoidance, which has been associated with generalized anxiety disorder. We also investigated whether the 5-HT(1A) and 5-HT(2A) receptors in the DPAG mediate the behavioral consequences induced by the injection of WAY-100635 into the DRN. RESULTS: Intra-DRN injection of WAY-100635 facilitated inhibitory avoidance, while impairing escape. The same effect was obtained after intra-DRN injection of the glutamate receptor agonist kainic acid. Preadministration of WAY-100635 into the DPAG counteracted the effect induced by intra-DRN injection of WAY-100635 and of kainic acid on escape, but not on inhibitory avoidance. Preadministration of the preferential 5-HT(2A) receptor antagonist ketanserin into the DPAG abolished the effects of intra-DRN injection of WAY-100635 on both elevated T-maze tasks. CONCLUSION: The results are indicative that 5-HT(1A) autoreceptors in the DRN are under tonic inhibitory influence by endogenous 5-HT. The effects of 5-HT release in the DPAG after intra-DRN injection of WAY-100635 and kainic acid on inhibitory avoidance and escape involve different 5-HT receptor subtypes. Whereas 5-HT(2A) receptors in the DPAG seem to mediate the effect of 5-HT on both behaviors, 5-HT(1A) receptors are only involved in the regulation of escape.
RATIONALE: It has been proposed that the serotonergic pathway that connects the dorsal raphe nucleus (DRN) to the dorsal periaqueductal gray (DPAG) is implicated in the regulation of escape, a behavior that has been related to panic. OBJECTIVES: We further evaluated this hypothesis by investigating whether intra-DRN injection of the 5-HT(1A) receptor antagonist WAY-100635 changes the escape response of rats submitted to the elevated T-maze. This test also measures inhibitory avoidance, which has been associated with generalized anxiety disorder. We also investigated whether the 5-HT(1A) and 5-HT(2A) receptors in the DPAG mediate the behavioral consequences induced by the injection of WAY-100635 into the DRN. RESULTS: Intra-DRN injection of WAY-100635 facilitated inhibitory avoidance, while impairing escape. The same effect was obtained after intra-DRN injection of the glutamate receptor agonist kainic acid. Preadministration of WAY-100635 into the DPAG counteracted the effect induced by intra-DRN injection of WAY-100635 and of kainic acid on escape, but not on inhibitory avoidance. Preadministration of the preferential 5-HT(2A) receptor antagonist ketanserin into the DPAG abolished the effects of intra-DRN injection of WAY-100635 on both elevated T-maze tasks. CONCLUSION: The results are indicative that 5-HT(1A) autoreceptors in the DRN are under tonic inhibitory influence by endogenous 5-HT. The effects of 5-HT release in the DPAG after intra-DRN injection of WAY-100635 and kainic acid on inhibitory avoidance and escape involve different 5-HT receptor subtypes. Whereas 5-HT(2A) receptors in the DPAG seem to mediate the effect of 5-HT on both behaviors, 5-HT(1A) receptors are only involved in the regulation of escape.
Authors: Lígia Moreiras Sena; Cíntia Bueno; Roger L H Pobbe; Telma G C S Andrade; Hélio Zangrossi; Milena B Viana Journal: Behav Brain Res Date: 2003-06-16 Impact factor: 3.332
Authors: Wayne E Pratt; Kara A Clissold; Peagan Lin; Amanda E Cain; Alexa F Ciesinski; Thomas R Hopkins; Adeolu O Ilesanmi; Erin A Kelly; Zachary Pierce-Messick; Daniel S Powell; Ian A Rosner Journal: Brain Res Date: 2016-07-16 Impact factor: 3.252
Authors: Roger L H Pobbe; Helio Zangrossi; D Caroline Blanchard; Robert J Blanchard Journal: Eur Neuropsychopharmacol Date: 2010-05-31 Impact factor: 4.600