title: 5-HT(1A) and 5-HT(2A) receptors in the rat dorsal periaqueductal gray mediate the antipanic-like effect induced by the stimulation of serotonergic neurons in the dorsal raphe nucleus.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, Brazil.
authors.forename: Roger L H
authors.initials: RL
authors.lastname: Pobbe
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000818:Animals; D007608:Kainic Acid / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016584:Panic Disorder / Q000517:prevention & control*; D010487:Periaqueductal Gray / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*
chemical_list: D010879:Piperazines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D007650:Ketanserin; D007608:Kainic Acid