title: Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats.
abstract: BACKGROUND
  Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood.
  
  
  OBJECTIVE
  The present study evaluates the role of the serotonergic neurotransmission within the DPAG in the modulation of escape responses of rats chronically treated with CBD.
  
  
  METHODS
  Male Wistar rats received acute or repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the elevated T-maze (ETM). We also investigated if CBD effects on the ETM depend on facilitation of 5-HT1A-mediated neurotransmission in the DPAG. To this latter aim, we verified if these effects would be prevented by intra-DPAG injection of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol/0.2 μL). Also, we verified, by in vivo microdialysis, if CBD chronic treatment increases serotonin (5-HT) release and, by quantitative polymerase chain reaction, if there are changes in 5HT-1A or 5HT-2C mRNA expression in DPAG.
  
  
  RESULTS
  The results showed that repeated but not acute peripheral administration of CBD decreases escape responses in the ETM, suggesting a panicolytic effect. This treatment did not change 5HT-1A or 5-HT-2C receptor mRNA expression nor modify serotonin extracellular concentrations in the DPAG. CBD effects were prevented by DPAG injection of the 5-HT1A receptor antagonist.
  
  
  CONCLUSIONS
  Together, these findings suggest that repeated treatment with CBD induces anti-panic effects by acting on 5-HT1A receptors in DPAG.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 3900 Bandeirantes av., Monte Alegre, Ribeirão Preto, São Paulo, Brazil. allinecampos@usp.br
authors.forename: Alline Cristina
authors.initials: AC
authors.lastname: Campos
authors.forename: Vanessa
authors.initials: V
authors.lastname: de Paula Soares
authors.forename: Milene C
authors.initials: MC
authors.lastname: Carvalho
authors.forename: Frederico Rogerio
authors.initials: FR
authors.lastname: Ferreira
authors.forename: Maria Adrielle
authors.initials: MA
authors.lastname: Vicente
authors.forename: Marcus Lira
authors.initials: ML
authors.lastname: Brandão
authors.forename: Antonio Waldo
authors.initials: AW
authors.lastname: Zuardi
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
authors.forename: Francisco Silveira
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001931:Brain Mapping; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017551:Microdialysis; D016584:Panic Disorder / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D044282:Receptor, Serotonin, 5-HT1A; D002185:Cannabidiol; D012701:Serotonin