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Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats

The effects of hormone status and age on the development of tolerance to Δ(9)-THC were assessed in sham-operated (intact) or ovariectomized (OVX) female rats that received either intraperitoneal saline or 5.6 mg/kg of Δ(9)-THC daily from postnatal day (PD) 75–180 (early adulthood onward) or PD 35–14...

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Autores principales: Winsauer, Peter J., Filipeanu, Catalin M., Weed, Peter F., Sutton, Jessie L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488627/
https://www.ncbi.nlm.nih.gov/pubmed/26191005
http://dx.doi.org/10.3389/fphar.2015.00133
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author Winsauer, Peter J.
Filipeanu, Catalin M.
Weed, Peter F.
Sutton, Jessie L.
author_facet Winsauer, Peter J.
Filipeanu, Catalin M.
Weed, Peter F.
Sutton, Jessie L.
author_sort Winsauer, Peter J.
collection PubMed
description The effects of hormone status and age on the development of tolerance to Δ(9)-THC were assessed in sham-operated (intact) or ovariectomized (OVX) female rats that received either intraperitoneal saline or 5.6 mg/kg of Δ(9)-THC daily from postnatal day (PD) 75–180 (early adulthood onward) or PD 35–140 (adolescence onward). During this time, the four groups for each age (i.e., intact/saline, intact/THC, OVX/saline, and OVX/THC) were trained in a learning and performance procedure and dose-effect curves were established for Δ(9)-THC (0.56–56 mg/kg) and the cannabinoid type-1 receptor (CB1R) antagonist rimonabant (0.32–10 mg/kg). Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic Δ(9)-THC, all of the Δ(9)-THC groups developed tolerance. However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic Δ(9)-THC was initiated. There was no evidence of dependence in any of the groups. Hippocampal protein expression of CB1R, AHA1 (a co-chaperone of CB1R) and HSP90β (a molecular chaperone modulated by AHA-1) was affected more by OVX than chronic Δ(9)-THC; striatal protein expression was not consistently affected by either manipulation. Hippocampal brain-derived neurotrophic factor expression varied with age, hormone status, and chronic treatment. Thus, hormonal status differentially affects the development of tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning and performance behavior in adolescent, but not adult, female rats. These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity.
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spelling pubmed-44886272015-07-17 Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats Winsauer, Peter J. Filipeanu, Catalin M. Weed, Peter F. Sutton, Jessie L. Front Pharmacol Pharmacology The effects of hormone status and age on the development of tolerance to Δ(9)-THC were assessed in sham-operated (intact) or ovariectomized (OVX) female rats that received either intraperitoneal saline or 5.6 mg/kg of Δ(9)-THC daily from postnatal day (PD) 75–180 (early adulthood onward) or PD 35–140 (adolescence onward). During this time, the four groups for each age (i.e., intact/saline, intact/THC, OVX/saline, and OVX/THC) were trained in a learning and performance procedure and dose-effect curves were established for Δ(9)-THC (0.56–56 mg/kg) and the cannabinoid type-1 receptor (CB1R) antagonist rimonabant (0.32–10 mg/kg). Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic Δ(9)-THC, all of the Δ(9)-THC groups developed tolerance. However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic Δ(9)-THC was initiated. There was no evidence of dependence in any of the groups. Hippocampal protein expression of CB1R, AHA1 (a co-chaperone of CB1R) and HSP90β (a molecular chaperone modulated by AHA-1) was affected more by OVX than chronic Δ(9)-THC; striatal protein expression was not consistently affected by either manipulation. Hippocampal brain-derived neurotrophic factor expression varied with age, hormone status, and chronic treatment. Thus, hormonal status differentially affects the development of tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning and performance behavior in adolescent, but not adult, female rats. These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity. Frontiers Media S.A. 2015-07-02 /pmc/articles/PMC4488627/ /pubmed/26191005 http://dx.doi.org/10.3389/fphar.2015.00133 Text en Copyright © 2015 Winsauer, Filipeanu, Weed and Sutton. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Winsauer, Peter J.
Filipeanu, Catalin M.
Weed, Peter F.
Sutton, Jessie L.
Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats
title Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats
title_full Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats
title_fullStr Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats
title_full_unstemmed Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats
title_short Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats
title_sort hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (δ(9)-thc) on learning in female rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488627/
https://www.ncbi.nlm.nih.gov/pubmed/26191005
http://dx.doi.org/10.3389/fphar.2015.00133
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