title: Cannabinoid CB1 receptors in the dorsal hippocampus and prelimbic medial prefrontal cortex modulate anxiety-like behavior in rats: additional evidence.
abstract: Endocannabinoids (ECBs) such as anandamide (AEA) act by activating cannabinoid type 1 (CB1) or 2 (CB2) receptors. The anxiolytic effect of drugs that facilitate ECB effects is associated with increase in AEA levels in several encephalic areas, including the prefrontal cortex (PFC). Activation of CB1 receptors by CB1 agonists injected directly into these areas is usually anxiolytic. However, depending on the encephalic region being investigated and on the stressful experiences, opposite effects were observed, as reported in the ventral HIP. In addition, contradictory results have been reported after CB1 activation in the dorsal HIP (dHIP). Therefore, in the present paper we have attempted to verify if directly interfering with ECB metabolism/reuptake in the prelimbic (PL) portion of the medial PFC (MPFC) and dHIP would produce different effects in two conceptually distinct animal models: the elevated plus maze (EPM) and the Vogel conflict test (VCT). We observed that drugs which interfere with ECB reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced anxiolytic-like effect, in both the EPM and in the VCT via CB1 receptors, suggesting that CB1 signaling in these brain regions modulates defensive responses to both innate and learned threatening stimuli. This data further strengthens previous results indicating modulation of hippocampal and MPFC activity via CB1 by ECBs, which could be therapeutically targeted to treat anxiety disorders.
authors.affiliation: Pharmacology Department, Medical School of Ribeirão Preto - University of São Paulo (FMRP/USP), Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil. Electronic address: sabrinalisboa@usp.br.
authors.forename: Sabrina F
authors.initials: SF
authors.lastname: Lisboa
authors.affiliation: Pharmacology Department, Medical School of Ribeirão Preto - University of São Paulo (FMRP/USP), Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Borges
authors.affiliation: Pharmacology Department, Medical School of Ribeirão Preto - University of São Paulo (FMRP/USP), Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Nejo
authors.affiliation: Pharmacology Department, Medical School of Ribeirão Preto - University of São Paulo (FMRP/USP), Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Fassini
authors.affiliation: Pharmacology Department, Medical School of Ribeirão Preto - University of São Paulo (FMRP/USP), Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
authors.affiliation: Pharmacology Department, Medical School of Ribeirão Preto - University of São Paulo (FMRP/USP), Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Leonardo B
authors.initials: LB
authors.lastname: Resstel
mesh_terms: D000818:Animals; D001007:Anxiety / Q000473:pathology*; D001095:Arachidonic Acids / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013623:Tail / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D001095:Arachidonic Acids; D001549:Benzamides; D002219:Carbamates; D004791:Enzyme Inhibitors; D043884:Receptor, Cannabinoid, CB1; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C107594:N-(4-hydroxyphenyl)arachidonylamide
keywords: Anandamide; Anxiety; CB1 receptors; Dorsal hippocampus; Endocannabinoids; Prefrontal cortex