title: Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure.
abstract: The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT2Areceptor (5-HT2AR) dependent. Here, we further investigated how blockade of 5-HT2ARs in mice exposed to a novel open-field arena affects medial PFC activation and basolateral amygdala (BLA) reactivity. We used c-Fos immunoreactivity (IR) as a marker of neuronal activation and stereological quantification for obtaining the total number of c-Fos-IR neurons as a measure of regional activation. We further examined the impact of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin-treated animals, upholding its involvement in modulating averseness. Ketanserin did not affect the number of activated striatal-projecting BLA neurons (measured by number of Cholera Toxin b (CTb) retrograde labelled neurons also being c-Fos-IR) following CTb injection in the ventral striatum. These results support a role of 5-HT2AR activation in modulating mPFC and BLA activation during exposure to a novel environment, which may be interrelated. Conversely, 5-HT2AR blockade does not seem to affect the amygdala-striatal projection.
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark; Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
authors.forename: Mona El-Sayed
authors.initials: ME
authors.lastname: Hervig
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.
authors.forename: Nadja Cecilie Hvid
authors.initials: NCH
authors.lastname: Jensen
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.
authors.forename: Nadja Bredo
authors.initials: NB
authors.lastname: Rasmussen
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Rydbirk
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.
authors.forename: Mikkel Vestergaard
authors.initials: MV
authors.lastname: Olesen
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Hay-Schmidt
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Pakkenberg
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark. Electronic address: Susana.aznar.kleijn@regionh.dk.
authors.forename: Susana
authors.initials: S
authors.lastname: Aznar
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism / Q000502:physiology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D007650:Ketanserin
keywords: 5-HT2A receptor; Averseness; Brain mapping; Frontolimbic pathway; Serotonin; Stereology