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Pituitary Adenylate Cyclase‐Activating Polypeptide‐27 (PACAP‐27) in the Thalamic Paraventricular Nucleus Is Stimulated by Ethanol Drinking
Author(s) -
Gupta Anuranita,
Gargiulo Andrew T.,
Curtis Genevieve R.,
Badve Preeti S.,
Pandey Surya,
Barson Jessica R.
Publication year - 2018
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13826
Subject(s) - neuropeptide , medicine , immunohistochemistry , gene isoform , endocrinology , neurochemical , nucleus , adenylate kinase , pituitary adenylate cyclase activating peptide , chemistry , cyclase , biology , vasoactive intestinal peptide , stimulation , neuroscience , gene , receptor , biochemistry
Background The paraventricular nucleus of the thalamus ( PVT ) is a limbic brain structure that affects ethanol (Et OH ) drinking, but the neurochemicals transcribed in this nucleus that may participate in this behavior have yet to be fully characterized. The neuropeptide, pituitary adenylate cyclase‐activating polypeptide ( PACAP ), is known to be transcribed in other limbic areas and to be involved in many of the same behaviors as the PVT itself, possibly including Et OH drinking. It exists in 2 isoforms, PACAP ‐38 and PACAP ‐27, with the former expressed at higher levels in most brain regions. The purpose of this study was to characterize PACAP in the PVT and to assess its response to Et OH drinking. Methods First, Et OH ‐naïve, Sprague Dawley rats were examined using quantitative real‐time polymerase chain reaction (qPCR) and immunohistochemistry, to characterize PACAP mRNA and peptide throughout the rostrocaudal axis of the PVT . Next, Et OH ‐naïve, vGLUT 2‐ GFP transgenic mice were examined using immunohistochemistry, to identify the neurochemical phenotype of the PACAP ergic cells in the PVT . Finally, Long Evans rats were trained to drink 20% Et OH under the intermittent‐access paradigm and then examined with PCR and immunohistochemistry, to determine the effects of Et OH on endogenous PACAP in the PVT. Results Gene expression of PACAP was detected across the entire PVT , denser in the posterior than the anterior portion of this nucleus. The protein isoform, PACAP ‐27, was present in a high percentage of cell bodies in the PVT , again particularly in the posterior portion, while PACAP ‐38 was instead dense in fibers. All PACAP ‐27 + cells colabeled with glutamate, which itself was identified in the majority of PVT cells. Et OH drinking led to an increase in PACAP gene expression and in levels of PACAP ‐27 in individual cells of the PVT . Conclusions This study characterizes the PVT neuropeptide, PACAP , and its understudied protein isoform, PACAP ‐27, and demonstrates that it is involved in pharmacologically relevant Et OH drinking. This indicates that PACAP ‐27 should be further investigated for its possible role in Et OH drinking.