Evaluation of the relationship between the gene expression level of orexin-1 receptor in the rat blood and prefrontal cortex, novelty-seeking, and proneness to methamphetamine dependence: A candidate biomarker.
Administration, Oral
Amphetamine-Related Disorders
/ genetics
Animals
Central Nervous System Stimulants
/ metabolism
Exploratory Behavior
/ physiology
Gene Expression Regulation
Lymphocytes
/ drug effects
Male
Methamphetamine
/ metabolism
Orexin Receptors
/ genetics
Prefrontal Cortex
/ drug effects
RNA, Messenger
/ genetics
Rats
Rats, Wistar
Dependence
Gene expression
Methamphetamine
Novelty-Seeking
Orexin receptors
Journal
Peptides
ISSN: 1873-5169
Titre abrégé: Peptides
Pays: United States
ID NLM: 8008690
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
13
02
2019
revised:
19
06
2020
accepted:
06
07
2020
pubmed:
16
7
2020
medline:
1
7
2021
entrez:
16
7
2020
Statut:
ppublish
Résumé
previous studies have suggested that methamphetamine (METH) abuse may affect orexin regulation. However, the data regarding the relationship between the current level of orexin and the vulnerability to METH abuse are minimal. Here, we have investigated the correlation between the gene expression level of the orexin-1 receptor (OX1R) in the rat prefrontal cortex (PFC) and blood lymphocytes and susceptibility to METH dependence and its impact on novelty-seeking behavior. male Wistar rats were first examined for novelty-seeking behavior by the novel object recognition test, and the expression level of OX1R in their blood lymphocytes was evaluated by real-time PCR. Then, the susceptibility to METH abuse was investigated by voluntary METH oral consumption test. According to the amounts of METH consumption, the animals were divided into two groups of METH preferring and non-preferring. Half of the rats in each group were sacrificed, and the level of OX1R in their blood lymphocytes and PFC tissue was measured. The other half were sacrificed for the same reason after two weeks of drug abstinence. The indexes of novelty-seeking behavior were significantly higher in the METH- preferring group compared to the non-preferring animals. Furthermore, the expression level of OX1R in the blood lymphocytes and PFC in the preferring group was considerably higher than the non-preferring group. Up-regulation of the mRNA expression level of OX1R in the lymphocytes and PFC may predict vulnerability to the METH consumption and novelty-seeking, which may serve as a potential biomarker for METH abuse.
Sections du résumé
BACKGROUND
previous studies have suggested that methamphetamine (METH) abuse may affect orexin regulation. However, the data regarding the relationship between the current level of orexin and the vulnerability to METH abuse are minimal. Here, we have investigated the correlation between the gene expression level of the orexin-1 receptor (OX1R) in the rat prefrontal cortex (PFC) and blood lymphocytes and susceptibility to METH dependence and its impact on novelty-seeking behavior.
METHODS
male Wistar rats were first examined for novelty-seeking behavior by the novel object recognition test, and the expression level of OX1R in their blood lymphocytes was evaluated by real-time PCR. Then, the susceptibility to METH abuse was investigated by voluntary METH oral consumption test. According to the amounts of METH consumption, the animals were divided into two groups of METH preferring and non-preferring. Half of the rats in each group were sacrificed, and the level of OX1R in their blood lymphocytes and PFC tissue was measured. The other half were sacrificed for the same reason after two weeks of drug abstinence.
RESULTS
The indexes of novelty-seeking behavior were significantly higher in the METH- preferring group compared to the non-preferring animals. Furthermore, the expression level of OX1R in the blood lymphocytes and PFC in the preferring group was considerably higher than the non-preferring group.
CONCLUSION
Up-regulation of the mRNA expression level of OX1R in the lymphocytes and PFC may predict vulnerability to the METH consumption and novelty-seeking, which may serve as a potential biomarker for METH abuse.
Identifiants
pubmed: 32668268
pii: S0196-9781(20)30117-0
doi: 10.1016/j.peptides.2020.170368
pii:
doi:
Substances chimiques
Central Nervous System Stimulants
0
Hcrtr1 protein, rat
0
Orexin Receptors
0
RNA, Messenger
0
Methamphetamine
44RAL3456C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
170368Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflict of interest.