title: Disinhibition of the rat prelimbic cortex promotes serotonergic activation of the dorsal raphe nucleus and panicolytic-like behavioral effects.
abstract: Several studies have shown that serotonin plays a dual role in the modulation of defensive behaviors related to anxiety and panic. A major source of serotonergic projections to limbic structures responsible for this modulation is the dorsal raphe nucleus (DR). Anatomical studies indicate that the prelimbic (PL) cortex sends dense glutamatergic projections to the DR, leading to stimulation or inhibition of serotonin release in structures innervated by the DR. The objective of the present study was to investigate if GABAergic disinhibition of the PL by means of local administration of picrotoxin (PIC), a chloride channel blocker, can affect serotonergic tone and the expression of defensive behaviors related to anxiety and panic. We used the elevated T-maze model and Vogel conflict test to evaluate defensive responses associated with anxiety or panic. The results showed that intra-PL PIC caused an increase in c-Fos activation in serotonergic cells in DR subregions. Furthermore, the intra-PL injection of PIC induced a panicolytic-like effect without affecting behaviors associated with anxiety. Our findings suggest that the PL-DR pathway, through DR serotonergic stimulation, is involved in the control of panic-related behaviors by control of serotonin release in structures that modulate panic responses, such as the dorsal periaqueductal gray.
authors.affiliation: 1 Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.|2 Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Paula Sm
authors.initials: PS
authors.lastname: Yamashita
authors.affiliation: 1 Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Ailton
authors.initials: A
authors.lastname: Spiacci
authors.affiliation: 2 Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Hassel
authors.affiliation: 2 Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
authors.affiliation: 1 Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Helio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001008:Anxiety Disorders / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000378:metabolism*; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D008297:Male; D010200:Panic / Q000502:physiology; D016584:Panic Disorder / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D010852:Picrotoxin; D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; D005680:gamma-Aminobutyric Acid
keywords: Panic; dorsal raphe nucleus; elevated T-maze; prefrontal cortex; serotonin