title: Activation of type 4 dopaminergic receptors in the prelimbic area of medial prefrontal cortex is necessary for the expression of innate fear behavior.
abstract: The prelimbic area (PL) of the medial Prefrontal cortex (mPFC) is involved in the acquisition and expression of conditioned and innate fear. Both types of fear share several neuronal pathways. It has been documented that dopamine (DA) plays an important role in the regulation of aversive memories in the mPFC. The exposure to an aversive stimulus, such as the smell of a predator odor or the exposure to footshock stress is accompanied by an increase in mPFC DA release. Evidence suggests that the type 4 dopaminergic receptor (D4R) is the molecular target through which DA modulates fear expression. In fact, the mPFC is the brain region with the highest expression of D4R; however, the role of D4R in the expression of innate fear has not been fully elucidated. Therefore, the principal objective of this work was to evaluate the participation of mPFC D4R in the expression of innate fear. Rats were exposed to the elevated plus-maze (EPM) and to the cat odor paradigm after the intra PL injection of L-745,870, selective D4R antagonist, to measure the expression of fear-related behaviors. Intra PL injection of L-745,870 increased the time spent in the EPM open arms and decreased freezing behavior in the cat odor paradigm. Our results also showed that D4R is expressed in GABAergic and pyramidal neurons in the PL region of PFC. Thus, D4R antagonism in the PL decreases the expression of innate fear-behavior indicating that the activation of D4R in the PL is necessary for the expression of innate fear-behavior.
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Macarena D
authors.initials: MD
authors.lastname: Vergara
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Victor N
authors.initials: VN
authors.lastname: Keller
authors.affiliation: Department of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: jfuentea@uc.cl.
authors.forename: José A
authors.initials: JA
authors.lastname: Fuentealba
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: kgysling@bio.puc.cl.
authors.forename: Katia
authors.initials: K
authors.lastname: Gysling
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000008:administration & dosage; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D059330:GABAergic Neurons / Q000378:metabolism; D008297:Male; D009812:Odorants; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
chemical_list: C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D018492:Dopamine Antagonists; D011725:Pyridines; D011758:Pyrroles; D050638:Receptors, Dopamine D4
keywords: Anxiety; Cat odor; Dopamine; Innate fear; Prefrontal cortex