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

Custodio, Raly James Perez; Sayson, Leandro Val; Botanas, Chrislean Jun; Abiero, Arvie; Kim, Mi-Kyung; Lee, Hyun Jun; Ryu, Ho‐Sung; Lee, Yong Sup; Kim, Hee Jin; Cheong, Jae Hoon

doi:10.1177/0269881120936458

Cited by 15 publications

(19 citation statements)

References 51 publications

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“…Another class of NPS, properly of the dissociative type, is represented by derivative of phencyclidine (PCP) and ketamine, which are N-methyl D-aspartate (NMDA) receptor antagonists. Subjective effects associated with the intake of these drugs include dissociative-like effects, with alteration of the mood and thought, and schizophrenia-like effects [ 163 ].…”

Section: Resultsmentioning

confidence: 99%

“…Diphenidine further inhibits NET and DAT, while it is a less potent DAT inhibitor, but both do not mediate an efflux of monoamines [ 137 ]. N-Ethyl-1,2-diphenylethanamine (ephenidine) also acts selectively by blocking NMDA receptors with a higher potency than ketamine, though also interacting with NET and DAT, which might contribute to the behavioral profile of the drug [ 163 ].…”

Section: Resultsmentioning

confidence: 99%

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Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Giorgetti

Pascali

Fais

et al. 2021

Life

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Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Giorgetti

Pascali

Fais

et al. 2021

Life

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show abstract

“…Procedure: This method was based on previous studies with some modifications ( Kim et al ., 2019 ; Custodio et al ., 2020 ; Sayson et al ., 2020 ). The test consisted of three phases: (A) habituation (days 1-3) and pre-conditioning (day 4; 15 min), (B) conditioning (days 5-12; 30 min), and (C) post-conditioning (day 13; 15 min).…”

Section: Methodsmentioning

confidence: 99%

Differentially Expressed Genes in Period 2-Overexpressing Mice Striatum May Underlie Their Lower Sensitivity to Methamphetamine Addiction-Like Behavior

Sayson

Kim

Jeon

et al. 2022

Biomol Ther (Seoul)

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Previous reports have demonstrated that genetic mechanisms greatly mediate responses to drugs of abuse, including methamphetamine (METH). The circadian gene Period 2 ( Per2 ) has been previously associated with differential responses towards METH in mice. While the behavioral consequences of eliminating Per2 have been illustrated previously, Per2 overexpression has not yet been comprehensively described; although, Per2 -overexpressing ( Per2 OE) mice previously showed reduced sensitivity towards METH-induced addiction-like behaviors. To further elucidate this distinct behavior of Per2 OE mice to METH, we identified possible candidate biomarkers by determining striatal differentially expressed genes (DEGs) in both drug-naïve and METH-treated Per2 OE mice relative to wild-type (WT), through RNA sequencing. Of the several DEGs in drug naïve Per2 OE mice, we identified six genes that were altered after repeated METH treatment in WT mice, but not in Per2 OE mice. These results, validated by quantitative real-time polymerase chain reaction, could suggest that the identified DEGs might underlie the previously reported weaker METH-induced responses of Per2 OE mice compared to WT. Gene network analysis also revealed that Asic3 , Hba-a1 , and Rnf17 are possibly associated with Per2 through physical interactions and predicted correlations, and might potentially participate in addiction. Inhibiting the functional protein of Asic3 prior to METH administration resulted in the partial reduction of METH-induced conditioned place preference in WT mice, supporting a possible involvement of Asic3 in METH-induced reward. Although encouraging further investigations, our findings suggest that these DEGs, including Asic3 , may play significant roles in the lower sensitivity of Per2 OE mice to METH.

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“…EEG was performed to assess theta waves in mice according to our previous study 80 , 81 . Briefly, a tethered, three-channel system head-mount (8200-K3-iS/iSE; Pinnacle Technology, Inc., Lawrence, KS) was implanted, secured with two stainless steel screws positioned frontally (A/P: −1.0 mm; M/L, −1.5 mm) and posteriorly (A/P: −1.0 mm; M/L, ±1.5 mm), and fixed with cement.…”

Section: Methodsmentioning

confidence: 99%

Low striatal T3 is implicated in inattention and memory impairment in an ADHD mouse model overexpressing thyroid hormone-responsive protein

et al. 2021

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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder, potentially with a biological basis; however, its exact cause remains unknown. Thyroid hormone (TH) abnormalities are more prevalent in patients with ADHD than in the general population, indicating a shared pathogenetic mechanism for these conditions. Previously, we identified that overexpression of thyroid hormone-responsive protein (THRSP), a gene highly responsive to TH status, induced inattention in male mice. Herein, we sought to explore whether TH function in THRSP-overexpressing (THRSP OE) mice influences ADHD-like (inattention) behavior. We now confirm that THRSP overexpression in male mice reproduces behavioral features of ADHD, including sustained inattention and memory impairment, accompanied by excessive theta waves that were found normal in both the THRSP-knockout and hetero groups. Physiological characterization revealed low striatal T3 levels in the THRSP OE mice due to reduced striatal T3-specific monocarboxylate transporter 8 (MCT8), indicating brain-specific hypothyroidism in this transgenic mouse strain. TH replacement for seven days rescued inattention and memory impairment and the normalization of theta waves. This study further supports the involvement of the upregulated THRSP gene in ADHD pathology and indicates that THRSP OE mice can serve as an animal model for the predominantly inattentive subtype of ADHD.

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

Cited by 15 publications

References 51 publications

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Differentially Expressed Genes in Period 2-Overexpressing Mice Striatum May Underlie Their Lower Sensitivity to Methamphetamine Addiction-Like Behavior

Low striatal T3 is implicated in inattention and memory impairment in an ADHD mouse model overexpressing thyroid hormone-responsive protein

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