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1,094 results on '"JANG, CHOON-GON"'

28. The neuropharmacological properties of α‐pyrrolidinobutiothiophenone, a new synthetic cathinone, in rodents; role of the dopaminergic system.

Author

Kim, Oc‐Hee, Jeon, Kyung Oh, Kim, Gihyeon, Jang, Choon‐Gon, Yoon, Seong Shoon, and Jang, Eun Young

Subjects
SYNTHETIC cathinone, DOPAMINE receptors, SYNTHETIC receptors, CHEMICAL derivatives, CATHINONE, METHAMPHETAMINE, RATS, DOPAMINE
Abstract

Background and Purpose: α‐Pyrrolidinobutiothiophenone (α‐PBT) is a chemical derivative of cathinone, a structural analogue of amphetamine. Until now, there have been a few previous neurochemical or neurobehavioural studies on the abuse potential of α‐PBT. Experimental Approach: We examined the abuse potential of α‐PBT by measuring psychomotor, rewarding, and reinforcing properties and methamphetamine‐like discriminative stimulus effects in rodents using locomotor activity, conditioned place preference, self‐administration, and drug discrimination studies. To clarify the underlying neuropharmacological mechanisms, we measured dopamine levels and neuronal activation in the dorsal striatum. In addition, we investigated the role of the dopamine D1 receptor or D2 receptors in α‐PBT‐induced hyperlocomotor activity, conditioned place preference, and the methamphetamine‐like discriminative stimulus effect of α‐PBT in rodents. Key Results: α‐PBT promoted hyperlocomotor activity in mice. α‐PBT induced drug‐paired place preference in mice and supported self‐administration in rats. In a drug discrimination experiment, α‐PBT fully substituted for the discriminative stimulus effects of methamphetamine in rats. Furthermore, α‐PBT increased dopamine levels and c‐Fos expression in the dorsal striatum of mice, which was associated with these behaviours. Finally, pretreatment with the D1 receptor antagonist SCH23390 or the D2 receptors antagonist eticlopride significantly attenuated acute or repeated α‐PBT‐induced hyperlocomotor activity, place preference, and the methamphetamine‐like discriminative stimulus effects in rodents. Conclusions and Implications: These findings suggest that α‐PBT has abuse potential at the highest dose tested via enhanced dopaminergic transmission in the dorsal striatum of rodents. The results provide scientific evidence for the legal restrictions of the recreational use of α‐PBT. [ABSTRACT FROM AUTHOR]

Published
2024
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29. The mutated cytoplasmic fragile X messenger ribonucleoprotein 1 (FMR1)‐interacting protein 2 (CYFIP2 S968F) regulates cocaine‐induced reward behaviour and plasticity in the nucleus accumbens.

Author

Kim, Young‐Jung, Kim, Kyungin, Lee, Youyoung, Min, Hee‐Won, Ko, Yong‐Hyun, Lee, Bo‐Ram, Hur, Kwang‐Hyun, Kim, Seon‐Kyung, Lee, Seok‐Yong, and Jang, Choon‐Gon

Subjects
NUCLEUS accumbens, PREFRONTAL cortex, PROTEIN expression, SENSITIZATION (Neuropsychology), COCAINE
Abstract

Background and Purpose: Cytoplasmic fragile X messenger ribonucleoprotein 1 (FMR1)‐interacting protein 2 (CYFIP2), as a component of the Wiskott–Aldrich syndrome protein family verprolin‐homologous protein (WAVE) regulatory complex, is involved in actin polymerization, contributing to neuronal development and structural plasticity. Mutating serine‐968 to phenylalanine (S968F) in CYFIP2 causes an altered cocaine response in mice. The neuronal mechanisms underlying this response remain unknown. Experimental Approach: We performed cocaine reward‐related behavioural tests and examined changes in synaptic protein phenotypes and neuronal morphology in the nucleus accumbens (NAc), using CYFIP2 S968F knock‐in mice to investigate the role of CYFIP2 in regulating cocaine reward. Key Results: CYFIP2 S968F mutation attenuated cocaine‐induced behavioural sensitization and conditioned place preference. Cocaine‐induced c‐Fos was not observed in the NAc of CYFIP2 S968F knock‐in mice. However, c‐Fos induction was still evident in the medial prefrontal cortex (mPFC). CYFIP2 S968F mutation altered cocaine‐associated CYFIP2 signalling, glutamatergic protein expression and synaptic density in the NAc following cocaine exposure. To further determine the role of CYFIP2 in NAc neuronal activity and the mPFC projecting to the NAc activity‐mediating reward response, we used optogenetic tools to stimulate the NAc or mPFC‐NAc pathway and observed that optogenetic activation of the NAc or mPFC‐NAc pathway induced reward‐related behaviours. This effect was not observed in the S968F mutation in CYFIP2. Conclusion and Implications: These results suggest that CYFIP2 plays a role in controlling cocaine‐mediated neuronal function and structural plasticity in the NAc, and that CYFIP2 could serve as a target for regulating cocaine reward. [ABSTRACT FROM AUTHOR]

Published
2024
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47. Transient receptor potential ankyrin 1 channel modulates the abuse‐related mechanisms of methamphetamine through interaction with dopamine transporter.

Author

Hur, Kwang‐Hyun, Lee, Youyoung, Donio, Audrey Lynn, Kim, Seon‐Kyung, Lee, Bo‐Ram, Seo, Jee‐Yeon, Kundu, Dooti, Kim, Kyeong‐Man, Kohut, Stephen J., Lee, Seok‐Yong, and Jang, Choon‐Gon

Subjects
METHAMPHETAMINE, DOPAMINE receptors, KNOCKOUT mice, DOPAMINE, NEURAL transmission, IMMUNOPRECIPITATION
Abstract

Background and Purpose: Methamphetamine (METH) use disorder has risen dramatically over the past decade, and there are currently no FDA‐approved medications due, in part, to gaps in our understanding of the pharmacological mechanisms related to METH action in the brain. Experimental Approach: Here, we investigated whether transient receptor potential ankyrin 1 (TRPA1) mediates each of several METH abuse‐related behaviours in rodents: self‐administration, drug‐primed reinstatement, acquisition of conditioned place preference, and hyperlocomotion. Additionally, METH‐induced molecular (i.e., neurotransmitter and protein) changes in the brain were compared between wild‐type and TRPA1 knock‐out mice. Finally, the relationship between TRPA1 and the dopamine transporter was investigated through immunoprecipitation and dopamine reuptake assays. Key Results: TRPA1 antagonism blunted METH self‐administration and drug‐primed reinstatement of METH‐seeking behaviour. Further, development of METH‐induced conditioned place preference and hyperlocomotion were inhibited by TRPA1 antagonist treatment, effects that were not observed in TRPA1 knock‐out mice. Similarly, molecular studies revealed METH‐induced increases in dopamine levels and expression of dopamine system‐related proteins in wild‐type, but not in TRPA1 knock‐out mice. Furthermore, pharmacological blockade of TRPA1 receptors reduced the interaction between TRPA1 and the dopamine transporter, thereby increasing dopamine reuptake activity by the transporter. Conclusion and Implications: This study demonstrates that TRPA1 is involved in the abuse‐related behavioural effects of METH, potentially through its modulatory role in METH‐induced activation of dopaminergic neurotransmission. Taken together, these data suggest that TRPA1 may be a novel therapeutic target for treating METH use disorder. [ABSTRACT FROM AUTHOR]

Published
2024
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