Effects of circadian disruption on methamphetamine consumption in methamphetamine-exposed rats

Doyle, Susan E.; Feng, Hanting; Garber, Garrett; Menaker, Michael; Lynch, Wendy J.

doi:10.1007/s00213-014-3845-2

Cited by 20 publications

(6 citation statements)

References 54 publications

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“…Furthermore, people with perturbations of the circadian system [e.g., shift-workers, people experiencing frequent jet-lags; ( 10 )], or animal models with disruptions of the body clock [e.g., chronic jet-lag exposure; ( 11 )] show an increase of drug intake (e.g., psychostimulants). For example, shift-workers use methamphetamine to avoid sleepiness and perform tasks accurately during their working hours.…”

Section: The Clock On Drugsmentioning

confidence: 99%

Insights into the Role of the Habenular Circadian Clock in Addiction

Salaberry

Mendoza

2016

Front. Psychiatry

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Drug addiction is a brain disease involving alterations in anatomy and functional neural communication. Drug intake and toxicity show daily rhythms in both humans and rodents. Evidence concerning the role of clock genes in drug intake has been previously reported. However, the implication of a timekeeping brain locus is much less known. The epithalamic lateral habenula (LHb) is now emerging as a key nucleus in drug intake and addiction. This brain structure modulates the activity of dopaminergic neurons from the ventral tegmental area, a central part of the reward system. Moreover, the LHb has circadian properties: LHb cellular activity (i.e., firing rate and clock genes expression) oscillates in a 24-h range, and the nucleus is affected by photic stimulation and has anatomical connections with the main circadian pacemaker, the suprachiasmatic nucleus. Here, we describe the current insights on the role of the LHb as a circadian oscillator and its possible implications on the rhythmic regulation of the dopaminergic activity and drug intake. These data could inspire new strategies to treat drug addiction, considering circadian timing as a principal factor.

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Section: The Clock On Drugsmentioning

confidence: 99%

Insights into the Role of the Habenular Circadian Clock in Addiction

Salaberry

Mendoza

2016

Front. Psychiatry

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“…These data suggest that MA effects on circadian rhythm may also be protective against MA consumption (Olsen et al, 2013 ). We have not examined whether circadian rhythm disturbance might alter MA intake, but a recent study by Doyle et al ( 2015 ) reported that MA consumption was increased in phase-shifted rats that had a history of MA use.…”

Section: Development Of An Animal Model Of Genetic Risk For Ma Intakementioning

confidence: 99%

An animal model of differential genetic risk for methamphetamine intake

Phillips

Shabani

2015

Front. Neurosci.

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The question of whether genetic factors contribute to risk for methamphetamine (MA) use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate gene studies provide strong support for a trace amine-associated receptor 1 gene, Taar1, polymorphism in risk for MA intake. MA is a trace amine-associated receptor 1 (TAAR1) agonist, and a non-functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1 function has the potential to increase risk for MA use. Overall, existing findings support the MA drinking lines as a powerful model for identifying genetic factors involved in determining risk for harmful MA use. Future directions include the development of a binge model of MA intake, examining the effect of withdrawal from chronic MA on MA intake, and studying potential Taar1 gene × gene and gene × environment interactions. These and other studies are intended to improve our genetic model with regard to its translational value to human addiction.

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“…Second, circadian rhythm disorders increase susceptibility to addiction. Repeated light/dark conversion can increase alcohol intake (36) and the preference for MA (37) in pre-exposure-treated rats. In humans, epidemiological studies reported that shift work or jet lag was associated with increased smoking and alcohol consumption (38,39).…”

Section: Analysis Of Dmr Data Inferred the Role Of The Circadian Entrmentioning

confidence: 98%

Genome-Wide DNA Methylation Analysis in Male Methamphetamine Users With Different Addiction Qualities

Liu

Luo²,

Dong³

et al. 2020

Front. Psychiatry

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This paper aimed to explore the genome-wide DNA methylation status of methamphetamine (MA) abusers with different qualities to addiction and to identify differentially methylated candidate genes. A total of 207 male MA abusers with an MA abuse frequency of ≥10 times and an MA abuse duration of ≥1 year were assigned to the high MA addiction quality group (HMAQ group; 168 subjects who met the diagnostic criteria for MA dependence according to the DSM-IV) or to the low MA addictive quality group (LMAQ group; 39 subjects who did not meet the criteria for MA dependence). In addition 105 healthy controls were recruited. Eight HMAQ subjects, eight LMAQ subjects, and eight healthy controls underwent genome-wide DNA methylation scans with an Infinium Human Methylation 450 array (Illumina). The differentially methylated region (DMR) data were entered into pathway analysis, and the differentially methylated position (DMP) data were screened for candidate genes and verified by MethyLight qPCR with all samples. Seven specific pathways with an abnormal methylation status were identified, including the circadian entrainment, cholinergic synapse, glutamatergic synapse, retrograde endocannabinoid signaling, GABAergic synapse, morphine addiction and PI3K-Akt signaling pathways. SLC1A6, BHLHB9, LYNX1, CAV2, and PCSK9 showed differences in their methylation levels in the three groups. Only the number of methylated copies of CAV2 was significantly higher in the LMAQ group than in the HMAQ group. Our findings suggest that the circadian entrainment pathway and the caveolin-2 gene may play key roles in MA addiction quality. Further studies on their functions and mechanisms will help us to better understand the pathogenesis of MA addiction and to explore new targets for drug intervention.

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Effects of circadian disruption on methamphetamine consumption in methamphetamine-exposed rats

Cited by 20 publications

References 54 publications

Insights into the Role of the Habenular Circadian Clock in Addiction

Insights into the Role of the Habenular Circadian Clock in Addiction

An animal model of differential genetic risk for methamphetamine intake

Genome-Wide DNA Methylation Analysis in Male Methamphetamine Users With Different Addiction Qualities

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