title: Serotonin-2A receptor regulation of panic-like behavior in the rat dorsal periaqueductal gray matter: the role of GABA.
abstract: BACKGROUND
  Electrical stimulation of the dorsal periaqueductal gray (dPAG) evokes escape, a defensive response associated with panic attacks. Stimulation of 5-HT1A or 5-HT2A receptors in this midbrain area equally inhibits escape performance, even though at the molecular level these receptors cause opposite effects, i.e., activation of the former hyperpolarizes the cell membrane, while the latter excites it. A proposal has been made that 5-HT2A receptor agonists exert their inhibitory effect on escape by activating GABAergic interneurons located in the dPAG.
  
  
  OBJECTIVE
  In the present study, we evaluated this hypothesis by investigating whether previous intra-dPAG administration of the GABAA receptor antagonist bicuculline blocks the anti-escape effect caused by the local injection of different 5-HT2A/2C receptor agonists.
  
  
  RESULTS
  Intra-dPAG administration of 5-HT, the preferential 5-HT2A receptor agonist DOI, the nonselective 5-HT2C receptor agonist mCPP or the 5-HT2C receptor agonist RO 60-0175 significantly inhibited the escape reaction induced by electrical stimulation of the same brain area. In all cases, this panicolytic-like effect was blocked by previous microinjection of bicuculline. This GABAA antagonist, however, failed to antagonize the anti-escape effect caused by the 5-HT1A receptor agonist 8-OH-DPAT. The inhibitory effect caused by DOI, RO 60-0175, and mCPP was also blocked by previous intra-dPAG injection of the preferential 5-HT2A receptor antagonist ketanserin. Pre-administration of the 5-HT2C receptor antagonist SB-242084 in the dPAG did not block the anti-escape effect of RO 60-0175.
  
  
  CONCLUSIONS
  Stimulation of 5-HT2A but not 5-HT2C receptors in the dPAG causes a panicolytic-like effect that is mediated by facilitation of GABAergic neurotransmission.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil. thatianeolisergio@usp.br
authors.forename: Thatiane
authors.initials: T
authors.lastname: de Oliveira Sergio
authors.forename: Valquiria Camin
authors.initials: VC
authors.lastname: de Bortoli
authors.forename: Helio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D004924:Escape Reaction / Q000187:drug effects; D008297:Male; D010200:Panic / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects* / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline