The circadian gene, <i>Per2</i>, influences methamphetamine sensitization and reward through the dopaminergic system in the striatum of mice

Kim, Mi-Kyung; Custodio, Raly James Perez; Botanas, Chrislean Jun; Peña, June Bryan de la; Sayson, Leandro Val; Abiero, Arvie; Ryoo, Zae Young; Cheong, Jae Hoon; Kim, Hee Jin

doi:10.1111/adb.12663

Cited by 25 publications

(23 citation statements)

References 43 publications

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“…The behavioral assay consisted of four phases: habituation, drug treatment, drug abstinence, and drug challenge. The protocol used was in accordance with our previous studies (Custodio et al, 2019; Kim et al, 2018). During the first 2 days, mice ( n =8) were habituated to the apparatus for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Two newly-emerging substituted phenethylamines MAL and BOD induce differential psychopharmacological effects in rodents

et al. 2020

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Background: Recently, the recreational use of substituted phenethylamines has grown rapidly. Among these are 2-(3,5-dimethoxy-4-((2-methylallyl)oxy)phenyl)ethanamine (MAL) and 2-(2,5-dimethoxy-4-methylphenyl)-2-methoxyethan-1-amine (BOD). However, studies characterizing their abuse potential are still lacking. Aim: The purpose of this study was to investigate the abuse potential of MAL and BOD. Methods: The psychostimulant, reinforcing, and rewarding properties of MAL and BOD were analyzed using locomotor sensitization, self-administration, and conditioned place preference tests. Dopamine antagonists (i.e. SCH23390, haloperidol) were administered during conditioned place preference to evaluate the involvement of the mesolimbic dopamine system. Furthermore, dopamine-related protein expression in the nucleus accumbens and the ventral tegmental area was measured along with dopamine concentrations in the nucleus accumbens. Electroencephalography was conducted to determine effects of MAL and BOD on brain wave activity. Results: MAL induced psychostimulant effects and sensitization, while BOD induced locomotor depression in mice. Only MAL was self-administered by rats. Both drugs induced conditioned place preference in mice at different doses; dopamine receptor antagonists blocked MAL- and BOD-induced conditioned place preference. Both the compounds altered the expression of dopamine receptor D1 and D2 proteins in the nucleus accumbens and tyrosine hydroxylase (TH) and dopamine transporter in the ventral tegmental area, enhanced dopamine levels in the nucleus accumbens, and increased delta and gamma wave activities in the brain. Conclusions: MAL may induce abuse potential via the mesolimbic dopaminergic system and possibly accompanied by alterations in brain wave activity. Moreover, the lack of rewarding and reinforcing effects in BOD suggest that this drug may have little to no capability to engender compulsive behavior, though having found to induce alterations in dopaminergic system and brain wave activities.

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Section: Methodsmentioning

confidence: 99%

Two newly-emerging substituted phenethylamines MAL and BOD induce differential psychopharmacological effects in rodents

et al. 2020

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“…The conditioned place preference (CPP) and self‐administration (SA) paradigms are experimental procedures widely used to investigate the abuse potential of drugs by characterizing their rewarding and reinforcing effects 12 . The CPP gauges the rewarding value of a drug by measuring the time spent in a drug‐paired compartment versus the time spent in a vehicle (VEH)‐paired compartment 13–15 . Moreover, the SA test assesses the reinforcing effects of a drug by counting the lever responses resulting in drug infusion 16 .…”

Section: Introductionmentioning

confidence: 99%

“…12 The CPP gauges the rewarding value of a drug by measuring the time spent in a drug-paired compartment versus the time spent in a vehicle (VEH)-paired compartment. [13][14][15] Moreover, the SA test assesses the reinforcing effects of a drug by counting the lever responses resulting in drug infusion. 16 Generally, drugs that stimulate the mesolimbic dopamine system induce CPP and/or SA.…”

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confidence: 99%

25B‐NBOMe, a novel N‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential

et al. 2019

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An increasing number of N-2-methoxybenzyl-phenethylamine (NBOMe) derivatives are being misused worldwide, including the potent hallucinogen 2-(4-bromo-2,5dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe). However, the number of studies characterizing the abuse potential and psychopharmacological properties of 25B-NBOMe is limited; thus, we examined its rewarding and reinforcing effects using conditioned place preference (CPP) and self-administration (SA) tests. Pretreatment with SCH23390 (SCH), Haloperidol (HAL), and ketanserin (KS), antagonists of dopamine D1 (DRD 1), dopamine D2 (DRD 2), and serotonin 2A (5-HT 2A receptor) receptors, respectively, was utilized during a CPP test to investigate the involvement of the dopaminergic and serotonergic systems in 25B-NBOMemediated effects. We also examined the effects of 25B-NBOMe on the expression of dopamine-related proteins in the nucleus accumbens (NAcc) and ventral tegmental area (VTA). Then, we measured the dopamine level, phosphorylated CREB (p-CREB), deltaFosB (ΔFosB), and brain-derived neurotrophic factor (BDNF) in the NAcc. In addition, we explored the involvement of 5-HT 2A receptors in the 25B-NBOMeinduced head twitch response (HTR). We also examined the effects of 25B-NBOMe on brain wave activity using electroencephalography. 25B-NBOMe elicited CPP and SA. SCH and HAL blocked 25B-NBOMe-induced CPP, whereas KS did not. Moreover, 25B-NBOMe altered the DRD 1 , DRD 2 , and dopamine transporter expression and increased dopamine levels. It also induced changes in p-CREB, ΔFosB, and BDNF expression. 25B-NBOMe induced HTR and increased 5-HT 2A receptor mRNA levels, effects inhibited by KS. Furthermore, 25B-NBOMe altered delta and gamma wave activity, which was normalized by SCH and HAL. These findings show Raly James Perez Custodio and Leandro Val Sayson have contributed equally to this manuscript.

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“…MAO is rhythmically expressed in wild-type larvae and upregulated in per1b mutant larvae (Huang et al 2015). Kim et al studied the influence of Per2 in cases of methamphetamine addiction and observed that Per2-overexpressed mice presented lower dopamine levels compared to Per2-knockout mice, suggesting that Per2 may influence the addictive effects of methamphetamine through the dopaminergic system (Kim, 2019). Bussi et al studied interval timing (duration discrimination within the seconds-to-minutes range), which involves the dopaminergic-glutamatergic pathway.…”

Section: Discussionmentioning

confidence: 99%

Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

et al. 2021

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A link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.

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The circadian gene, Per2, influences methamphetamine sensitization and reward through the dopaminergic system in the striatum of mice

Cited by 25 publications

References 43 publications

Two newly-emerging substituted phenethylamines MAL and BOD induce differential psychopharmacological effects in rodents

Two newly-emerging substituted phenethylamines MAL and BOD induce differential psychopharmacological effects in rodents

25B‐NBOMe, a novel N‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential

Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

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