Genetic blockade of the dopamine D<inf>3</inf> receptor enhances hippocampal expression of PACAP and receptors and alters their cortical distribution

Marzagalli, R; Leggio, GM; Bucolo, C; Pricoco, E; Keay, KA; Cardile, V; Castorina, S; Salomone, S; Drago, F; Castorina, A

Genetic blockade of the dopamine D<inf>3</inf> receptor enhances hippocampal expression of PACAP and receptors and alters their cortical distribution

Marzagalli, R Leggio, GM Bucolo, C Pricoco, E Keay, KA Cardile, V Castorina, S Salomone, S Drago, F Castorina, A

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Publication Type:: Journal Article
Citation:: Neuroscience, 2016, 316 pp. 279 - 295
Issue Date:: 2016-03-01

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Field	Value	Language
dc.contributor.author	Marzagalli, R	en_US
dc.contributor.author	Leggio, GM	en_US
dc.contributor.author	Bucolo, C	en_US
dc.contributor.author	Pricoco, E	en_US
dc.contributor.author	Keay, KA	en_US
dc.contributor.author	Cardile, V	en_US
dc.contributor.author	Castorina, S	en_US
dc.contributor.author	Salomone, S	en_US
dc.contributor.author	Drago, F	en_US
dc.contributor.author	Castorina, A https://orcid.org/0000-0001-7037-759X	en_US
dc.date.available	2015-12-17	en_US
dc.date.issued	2016-03-01	en_US
dc.identifier.citation	Neuroscience, 2016, 316 pp. 279 - 295	en_US
dc.identifier.issn	0306-4522	en_US
dc.identifier.uri	http://hdl.handle.net/10453/90084
dc.description.abstract	© 2015 IBRO. Dopamine D3 receptors (D3Rs) are implicated in several aspects of cognition, but their role in aversive conditioning has only been marginally uncovered. Investigations have reported that blockade of D3Rs enhances the acquisition of fear memories, a phenomenon tightly linked to the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP). However, the impact of D3R ablation on the PACAPergic system in regions critical for the formation of new memories remains unexplored. To address this issue, levels of PACAP and its receptors were compared in the hippocampus and cerebral cortex (CX) of mice devoid of functional D3Rs (D3R-/-) and wild-types (WTs) using a series of comparative immunohistochemical and biochemical analyses. Morphometric and stereological data revealed increased hippocampal area and volume in D3R-/- mice, and augmented neuronal density in CA1 and CA2/3 subfields. PACAP levels were increased in the hippocampus of D3R-/- mice. Expression of PACAP receptors was also heightened in mutant mice. In the CX, PACAP immunoreactivity (IR), was restricted to cortical layer V in WTs, but was distributed throughout layers IV-VI in D3R-/- mice, along with increased mRNAs, protein concentration and staining scores. Consistently, PAC1, VPAC1 and VPAC2 IRs were variably redistributed in CX, with a general upregulation in cortical layers II-IV in knockout animals. Our interpretation of these findings is that disturbed dopamine neurotransmission due to genetic D3R blockade may enhance the PACAP/PAC1-VPAC axis, a key endogenous system for the processing of fear memories. This could explain, at least in part, the facilitated acquisition and consolidation of aversive memories in D3R-/- mice.	en_US
dc.relation.ispartof	Neuroscience	en_US
dc.relation.isbasedon	10.1016/j.neuroscience.2015.12.034	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Hippocampus	en_US
dc.subject.mesh	Cerebral Cortex	en_US
dc.subject.mesh	Neurons	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice, Transgenic	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Analysis of Variance	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Receptors, Dopamine D3	en_US
dc.subject.mesh	Pituitary Adenylate Cyclase-Activating Polypeptide	en_US
dc.subject.mesh	Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide	en_US
dc.subject.mesh	Receptors, Vasoactive Intestinal Polypeptide, Type I	en_US
dc.subject.mesh	Receptors, Vasoactive Intestinal Peptide, Type II	en_US
dc.subject.mesh	Neuroimaging	en_US
dc.title	Genetic blockade of the dopamine D<inf>3</inf> receptor enhances hippocampal expression of PACAP and receptors and alters their cortical distribution	en_US
dc.type	Journal Article
utslib.citation.volume	316	en_US
utslib.for	1701 Psychology	en_US
utslib.for	170101 Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1702 Cognitive Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.publication-status	Published	en_US
pubs.volume	316	en_US

Abstract:

© 2015 IBRO. Dopamine D3 receptors (D3Rs) are implicated in several aspects of cognition, but their role in aversive conditioning has only been marginally uncovered. Investigations have reported that blockade of D3Rs enhances the acquisition of fear memories, a phenomenon tightly linked to the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP). However, the impact of D3R ablation on the PACAPergic system in regions critical for the formation of new memories remains unexplored. To address this issue, levels of PACAP and its receptors were compared in the hippocampus and cerebral cortex (CX) of mice devoid of functional D3Rs (D3R-/-) and wild-types (WTs) using a series of comparative immunohistochemical and biochemical analyses. Morphometric and stereological data revealed increased hippocampal area and volume in D3R-/- mice, and augmented neuronal density in CA1 and CA2/3 subfields. PACAP levels were increased in the hippocampus of D3R-/- mice. Expression of PACAP receptors was also heightened in mutant mice. In the CX, PACAP immunoreactivity (IR), was restricted to cortical layer V in WTs, but was distributed throughout layers IV-VI in D3R-/- mice, along with increased mRNAs, protein concentration and staining scores. Consistently, PAC1, VPAC1 and VPAC2 IRs were variably redistributed in CX, with a general upregulation in cortical layers II-IV in knockout animals. Our interpretation of these findings is that disturbed dopamine neurotransmission due to genetic D3R blockade may enhance the PACAP/PAC1-VPAC axis, a key endogenous system for the processing of fear memories. This could explain, at least in part, the facilitated acquisition and consolidation of aversive memories in D3R-/- mice.

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http://hdl.handle.net/10453/90084