title: Delta(9)-THC administered into the medial prefrontal cortex disrupts the spatial working memory.
abstract: BACKGROUND
  Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) disrupts working memory. The prefrontal cortex (PFC) is involved in the processing of working memory, and its medial portion (mPFC) is part of a brain reward circuit as constituted by the mesocorticolimbic dopaminergic system.
  
  
  OBJECTIVE
  This study examined the involvement of the mPFC in the effects of Delta(9)-THC on spatial working memory.
  
  
  METHODS
  Ten male Wistar rats well-trained in a radial arm maze and with bilateral cannula implanted in the mPFC received Delta(9)-THC intra-cortically (Delta(9)-THC IC) at doses of 0 (VEH), 32, 100 or 180 microg, 5 min before a 5-s or a 1-h delayed task in order to measure a short- or long-term spatial working memory, respectively. By contrast, 11 other animals received Delta(9)-THC intraperitoneally (Delta(9)-THC IP) at doses of 0 (VEH), 0.32, 1 or 1.8 mg/kg, 30 min before a 5-s or a 1-h delayed task. Additionally, after a 15-day washout, the effect of an IP or IC pre-exposure of Delta(9)-THC was examined by repeating both dose-effect curves in a crossover order for the routes of administration.
  
  
  RESULTS
  Delta(9)-THC IP produced significantly larger number of errors at doses of 0.32 or 1 mg/kg as compared to VEH in the 1-h post-delay performance. Delta(9)-THC 100 microg IC also produced significantly larger number of errors as compared to VEH and also to the other doses (32 or 180 microg) IC in the 1-h post-delay performance. Previous exposure to Delta(9)-THC IP or IC did not significantly affect the disruptive effect of this cannabinoid.
  
  
  CONCLUSIONS
  Delta(9)-THC administered directly in the mPFC impaired 1-h delayed task in the radial arm maze in a manner similar to that observed for its systemic administration, suggesting that the mPFC is involved in the disruptive effects of Delta(9)-THC on spatial working memory.
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Av. Marechal Campos, 1468, B. Maruípe, 29042-755 Vitória, ES, Brazil.
authors.forename: Lívia Carla
authors.initials: LC
authors.lastname: Silva de Melo
authors.forename: Ariane Pinheiro
authors.initials: AP
authors.lastname: Cruz
authors.forename: Saavedra José
authors.initials: SJ
authors.lastname: Rios Valentim
authors.forename: Andresa Rosane
authors.initials: AR
authors.lastname: Marinho
authors.forename: Josidéia Barreto
authors.initials: JB
authors.lastname: Mendonça
authors.forename: Ester Miyuki
authors.initials: EM
authors.lastname: Nakamura-Palacios
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D011619:Psychotropic Drugs; D013759:Dronabinol