Document Detail


Sex differences in U50,488H-induced phosphorylation of p44/42 mitogen-activated protein kinase in the guinea pig brain.
MedLine Citation:
PMID:  22863678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently there has been a widespread interest in the development of kappa opioid receptor (KOPR) ligands for treatment of pain, depression and anxiety, and prevention of stress-induced drug relapse. However, most of these preclinical studies have been conducted using male experimental animals. In the present study we examined if sex differences exist in neural activity induced by the KOPR agonist trans-(±)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl) benzeneacetamide methanesulfonate (U50,488H). Here, we used immunohistochemistry to detect activation (phosphorylation) of p44/42 mitogen-activated protein kinase (MAPK) as an indicator of neural activity. Following habituation to injection for 3 days, adult guinea pigs received a single injection of U50,488H (5mg/kg, s.c.) and perfused 30-45 min later. U50,488H-induced an increase in the number of cells immuno-positive for phosphorylated p44/42 MAPK in subregions of the amygdala, thalamus, paraventricular nucleus of the hypothalamus, periaqueductal gray, and dorsal raphe nuclei. In contrast, U50,488H-induced a decrease in immuno-positive cells in the ventrolateral and lateral orbital cortex. Pretreatment with the KOPR antagonist norbinaltorphimine (10mg/kg, i.p.) 18 h prior to U50,488H significantly reversed the effects of U50,488H in most regions. In addition, we observed a notable sex difference in the basolateral amygdala; in males, U50,488H induced an increase in immuno-positive cell numbers but a decrease in females. However, across other brain regions males were generally more sensitive to U50,488H-induced alterations than females. These results suggest the need to include female subjects in studies examining emotional responses to KOPR ligands.
Authors:
K Rasakham; K L McGillivray; L-Y Liu-Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-31
Journal Detail:
Title:  Neuroscience     Volume:  223     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-24     Completed Date:  2013-05-01     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  447-56     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States.
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MeSH Terms
Descriptor/Qualifier:
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology*
Analgesics, Non-Narcotic / pharmacology*
Animals
Brain / drug effects*,  enzymology
Brain Mapping
Female
Gene Expression Regulation, Enzymologic / drug effects
Guinea Pigs
Male
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Phosphorylation / drug effects
Sex Characteristics*
Grant Support
ID/Acronym/Agency:
DA17302/DA/NIDA NIH HHS; P30 DA013429/DA/NIDA NIH HHS; R01 DA017302/DA/NIDA NIH HHS; T32 DA 07237-20/DA/NIDA NIH HHS; T32 DA007237/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Analgesics, Non-Narcotic; 67198-13-4/3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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