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Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse

Prolonged use of methamphetamine (meth) has been associated with episodic memory deficits in humans, and preclinical rat models of meth self-administration indicate the memory deficits are a consequence of meth use. Others have suggested that the meth-induced memory deficits may promote a cyclical p...

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Autores principales: Peters, Jamie, Scofield, Michael D., Reichel, Carmela M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097768/
https://www.ncbi.nlm.nih.gov/pubmed/30115762
http://dx.doi.org/10.1101/lm.046797.117
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author Peters, Jamie
Scofield, Michael D.
Reichel, Carmela M.
author_facet Peters, Jamie
Scofield, Michael D.
Reichel, Carmela M.
author_sort Peters, Jamie
collection PubMed
description Prolonged use of methamphetamine (meth) has been associated with episodic memory deficits in humans, and preclinical rat models of meth self-administration indicate the memory deficits are a consequence of meth use. Others have suggested that the meth-induced memory deficits may promote a cyclical pattern of drug use, abstinence, and relapse, although preclinical evidence for this relationship is somewhat lacking. The memory deficits in preclinical models manifest as a loss of novel object recognition (NOR) memory. These deficits occur one to two weeks after cessation of meth use and involve the perirhinal cortex, a parahippocampal region essential to NOR memory. We hypothesized that a loss of perirhinal cortex function contributes to both the NOR memory deficits and increased vulnerability to relapse in a novel-cue reinstatement model. To test this, we attempted to restore NOR memory in meth rats using an excitatory Gq-DREADD in perirhinal neurons. Activation of these neurons not only reversed the meth-induced deficit in NOR memory, but also restored novelty salience in a novel-cue reinstatement model. Thus, perirhinal cortex functionality contributes to both memory deficits in relapse in a long-access model of meth self-administration in rats, and chemogenetic restoration of perirhinal function restores memory and reduces relapse.
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spelling pubmed-60977682019-09-01 Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse Peters, Jamie Scofield, Michael D. Reichel, Carmela M. Learn Mem Research Prolonged use of methamphetamine (meth) has been associated with episodic memory deficits in humans, and preclinical rat models of meth self-administration indicate the memory deficits are a consequence of meth use. Others have suggested that the meth-induced memory deficits may promote a cyclical pattern of drug use, abstinence, and relapse, although preclinical evidence for this relationship is somewhat lacking. The memory deficits in preclinical models manifest as a loss of novel object recognition (NOR) memory. These deficits occur one to two weeks after cessation of meth use and involve the perirhinal cortex, a parahippocampal region essential to NOR memory. We hypothesized that a loss of perirhinal cortex function contributes to both the NOR memory deficits and increased vulnerability to relapse in a novel-cue reinstatement model. To test this, we attempted to restore NOR memory in meth rats using an excitatory Gq-DREADD in perirhinal neurons. Activation of these neurons not only reversed the meth-induced deficit in NOR memory, but also restored novelty salience in a novel-cue reinstatement model. Thus, perirhinal cortex functionality contributes to both memory deficits in relapse in a long-access model of meth self-administration in rats, and chemogenetic restoration of perirhinal function restores memory and reduces relapse. Cold Spring Harbor Laboratory Press 2018-09 /pmc/articles/PMC6097768/ /pubmed/30115762 http://dx.doi.org/10.1101/lm.046797.117 Text en © 2018 Peters et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Peters, Jamie
Scofield, Michael D.
Reichel, Carmela M.
Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse
title Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse
title_full Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse
title_fullStr Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse
title_full_unstemmed Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse
title_short Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse
title_sort chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097768/
https://www.ncbi.nlm.nih.gov/pubmed/30115762
http://dx.doi.org/10.1101/lm.046797.117
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