Cargando…

Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)

Methamphetamine (METH) use disorder (MUD) is characterized by compulsive and repeated drug taking despite negative life consequences. Large intake of METH in humans and animals is accompanied by dysfunctions in learning and memory processes. The endocannabinoid system (ECS) is known to modulate syna...

Descripción completa

Detalles Bibliográficos
Autores principales: Jayanthi, Subramaniam, Peesapati, Ritvik, McCoy, Michael T., Ladenheim, Bruce, Cadet, Jean Lud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857101/
https://www.ncbi.nlm.nih.gov/pubmed/34978045
http://dx.doi.org/10.1007/s12035-021-02656-8
_version_ 1784653971578683392
author Jayanthi, Subramaniam
Peesapati, Ritvik
McCoy, Michael T.
Ladenheim, Bruce
Cadet, Jean Lud
author_facet Jayanthi, Subramaniam
Peesapati, Ritvik
McCoy, Michael T.
Ladenheim, Bruce
Cadet, Jean Lud
author_sort Jayanthi, Subramaniam
collection PubMed
description Methamphetamine (METH) use disorder (MUD) is characterized by compulsive and repeated drug taking despite negative life consequences. Large intake of METH in humans and animals is accompanied by dysfunctions in learning and memory processes. The endocannabinoid system (ECS) is known to modulate synaptic plasticity and cognitive functions. In addition, the ECS has been implicated in some of the manifestations of substance use disorders (SUDs). We therefore sought to identify potential changes in the expression of various enzymes and of the receptors (CB1 and CB2) that are members of that system. Herein, we used a model of METH self-administration (SA) that includes a punishment phase (footshocks) that helps to separate rats into a compulsive METH phenotype (compulsive) that continues to take METH and a non-compulsive METH (abstinent) group that suppressed or stopped taking METH. Animals were euthanized 2 h after the last METH SA session and their hippocampi were used to measure mRNA levels of cannabinoid receptors (CB/Cnr), as well as those of synthesizing (DAGL-A, DAGL-B, NAPEPLD) and metabolizing (MGLL, FAAH, PTGS2) enzymes of the endocannabinoid cascade. Non-compulsive rats exhibited significant increased hippocampal expression of CB1/Cnr1 and CB2/Cnr2 mRNAs. mRNA levels of the synthesizing enzyme, DAGL-A, and of the metabolic enzymes, MGLL and FAAH, were also increased. Non-compulsive rats also exhibited a significant decrease in hippocampal Ptgs2 mRNA levels. Taken together, these observations implicate the hippocampal endocannabinoid system in the suppression of METH intake in the presence of adverse consequences. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-021-02656-8.
format Online
Article
Text
id pubmed-8857101
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-88571012022-02-23 Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2) Jayanthi, Subramaniam Peesapati, Ritvik McCoy, Michael T. Ladenheim, Bruce Cadet, Jean Lud Mol Neurobiol Article Methamphetamine (METH) use disorder (MUD) is characterized by compulsive and repeated drug taking despite negative life consequences. Large intake of METH in humans and animals is accompanied by dysfunctions in learning and memory processes. The endocannabinoid system (ECS) is known to modulate synaptic plasticity and cognitive functions. In addition, the ECS has been implicated in some of the manifestations of substance use disorders (SUDs). We therefore sought to identify potential changes in the expression of various enzymes and of the receptors (CB1 and CB2) that are members of that system. Herein, we used a model of METH self-administration (SA) that includes a punishment phase (footshocks) that helps to separate rats into a compulsive METH phenotype (compulsive) that continues to take METH and a non-compulsive METH (abstinent) group that suppressed or stopped taking METH. Animals were euthanized 2 h after the last METH SA session and their hippocampi were used to measure mRNA levels of cannabinoid receptors (CB/Cnr), as well as those of synthesizing (DAGL-A, DAGL-B, NAPEPLD) and metabolizing (MGLL, FAAH, PTGS2) enzymes of the endocannabinoid cascade. Non-compulsive rats exhibited significant increased hippocampal expression of CB1/Cnr1 and CB2/Cnr2 mRNAs. mRNA levels of the synthesizing enzyme, DAGL-A, and of the metabolic enzymes, MGLL and FAAH, were also increased. Non-compulsive rats also exhibited a significant decrease in hippocampal Ptgs2 mRNA levels. Taken together, these observations implicate the hippocampal endocannabinoid system in the suppression of METH intake in the presence of adverse consequences. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-021-02656-8. Springer US 2022-01-03 2022 /pmc/articles/PMC8857101/ /pubmed/34978045 http://dx.doi.org/10.1007/s12035-021-02656-8 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jayanthi, Subramaniam
Peesapati, Ritvik
McCoy, Michael T.
Ladenheim, Bruce
Cadet, Jean Lud
Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)
title Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)
title_full Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)
title_fullStr Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)
title_full_unstemmed Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)
title_short Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)
title_sort footshock-induced abstinence from compulsive methamphetamine self-administration in rat model is accompanied by increased hippocampal expression of cannabinoid receptors (cb1 and cb2)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857101/
https://www.ncbi.nlm.nih.gov/pubmed/34978045
http://dx.doi.org/10.1007/s12035-021-02656-8
work_keys_str_mv AT jayanthisubramaniam footshockinducedabstinencefromcompulsivemethamphetamineselfadministrationinratmodelisaccompaniedbyincreasedhippocampalexpressionofcannabinoidreceptorscb1andcb2
AT peesapatiritvik footshockinducedabstinencefromcompulsivemethamphetamineselfadministrationinratmodelisaccompaniedbyincreasedhippocampalexpressionofcannabinoidreceptorscb1andcb2
AT mccoymichaelt footshockinducedabstinencefromcompulsivemethamphetamineselfadministrationinratmodelisaccompaniedbyincreasedhippocampalexpressionofcannabinoidreceptorscb1andcb2
AT ladenheimbruce footshockinducedabstinencefromcompulsivemethamphetamineselfadministrationinratmodelisaccompaniedbyincreasedhippocampalexpressionofcannabinoidreceptorscb1andcb2
AT cadetjeanlud footshockinducedabstinencefromcompulsivemethamphetamineselfadministrationinratmodelisaccompaniedbyincreasedhippocampalexpressionofcannabinoidreceptorscb1andcb2