Effects of repeated treatment with methcathinone, mephedrone, and fenfluramine on intracranial self-stimulation in rats

Suyama, Julie A.; Banks, Matthew L.; Negus, S. Stevens

doi:10.1007/s00213-018-5029-y

Cited by 19 publications

(14 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rats, substances that are selective for DAT vs. SERT facilitate dose-dependent and abuse-related intracranial self-stimulation, indicating high abuse potential. In contrast, substances that are selective for the SERT vs. DAT depress dose-dependent intracranial self-stimulation (Suyama et al 2019), indicating a lower risk of abuse. Repeated exposure to substances with similar activity at the DAT and SERT may sustain the expression of DAT-mediated abuse-related effects while developing tolerance to SERT-mediated abuse-limiting effects, thus resulting in a higher abuse potential (Suyama et al 2019).…”

Section: Stimulantsmentioning

confidence: 98%

“…In contrast, substances that are selective for the SERT vs. DAT depress dose-dependent intracranial self-stimulation (Suyama et al 2019), indicating a lower risk of abuse. Repeated exposure to substances with similar activity at the DAT and SERT may sustain the expression of DAT-mediated abuse-related effects while developing tolerance to SERT-mediated abuse-limiting effects, thus resulting in a higher abuse potential (Suyama et al 2019). The number of available designer stimulants is constantly increasing, and their use can cause various physiological complications…”

Section: Stimulantsmentioning

confidence: 98%

See 1 more Smart Citation

Designer drugs: mechanism of action and adverse effects

2020

View full text Add to dashboard Cite

Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at l-opioid receptors and c-aminobutyric acid-A (GABA A) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT 2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

show abstract

Section: Stimulantsmentioning

confidence: 98%

Section: Stimulantsmentioning

confidence: 98%

Designer drugs: mechanism of action and adverse effects

2020

View full text Add to dashboard Cite

show abstract

“…Specifically, we have identified three general profiles of ICSS effects that can occur during chronic treatment with drugs that produce primarily ICSS depression in drug-naïve subjects: (1) tolerance to ICSS depression and emergence of ICSS facilitation such as that described here with mu opioid receptor agonists or with high nicotine doses [18], (2) tolerance to ICSS depression without emergence of ICSS facilitation [e.g. with cannabinoid receptor agonists like ∆9-tetrahydrocannabinol [19,20], the N-methyl-D-aspartate glutamate receptor antagonist ketamine [21], the delta opioid receptor agonist SNC80 [22], and the serotonin releaser fenfluramine [23]], or (3) sustained ICSS depression [e.g. with the kappa agonist salvinorin A [24], the dopamine D2 agonist quinpirole [22], and the serotonin 5HT1A/2A receptor agonist flibanserin [25]].…”

Section: Effects Of Acute and Repeated Treatment With Systemic Morphinementioning

confidence: 99%

Determinants of opioid abuse potential: Insights using intracranial self-stimulation

Negus

Moerke

2019

Peptides

View full text Add to dashboard Cite

Intracranial self-stimulation (ICSS) is one procedure that can be used for preclinical abuse potential assessment. In ICSS procedures, subjects with microelectrodes implanted into a brainreward region are trained to press an operant response lever for pulses of electrical brain stimulation, and drugs are evaluated for their effectiveness to increase or "facilitate" ICSS responding (an abuse-related effect) or to depress ICSS responding (an abuse-limiting effect). ICSS has been used for decades to evaluate determinants of opioid abuse potential, and this article reviews pharmacological and biological determinants of opioid abuse potential as revealed by ICSS studies in rodents. One of the most important observations from ICSS studies is that abused mu opioid receptor (MOR) agonists like morphine often fail to produce abuse-related ICSS facilitation in opioid-naïve subjects, but several days of repeated opioid exposure is sufficient for opioid-induced facilitation to emerge. Future studies with ICSS could help (a) to clarify mechanisms that increase MOR agonist abuse potential during early opioid exposure or during chronic exposure leading to dependence, (b) to evaluate novel opioids either developed as candidate analgesics with reduced abuse potential or identified as designer opioids being synthesized and distributed for illicit use, and (c) to test candidate pharmacotherapies for treatment of opioid abuse in non-dependent and dependent subjects.

show abstract

“…Novel psychostimulant drugs are mostly classified on the basis of the greater noradrenergic vs. dopaminergic vs. serotoninergic activity [ 119 , 120 , 121 , 122 , 123 ]. Indeed, a high DAT/SERT ratio and a substrate-type monoamine releasers action is typical of amphetamine-type stimulant-like properties, with high potential of abuse [ 124 ], whereas a lower ratio (0.01–0.1) leads mainly to empathogenic effects, similarly to MDMA, with low intracranial self-stimulation [ 7 , 116 , 125 ]. The DAT/SERT ratios of the main stimulants are shown in Figure 3 .…”

Section: Resultsmentioning

confidence: 99%

“…Amphetamine-type psychostimulant include derivatives of aminorex, such as 4-methylaminorex (4-MAR) and 4,4′-dimethylaminorex (4,4′-DMAR) [ 133 , 134 ]. Although both are derivatives of aminorex, the former appears as a more typical stimulant, with a high DAT/SERT ratio, while the latter is thought to lead mainly to empathogenic effects [ 125 ].…”

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

View full text Add to dashboard Cite

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.

show abstract

Effects of repeated treatment with methcathinone, mephedrone, and fenfluramine on intracranial self-stimulation in rats

Abstract: Repeated exposure to mixed-action DAT≈SERT substrates such as mephedrone can result in increased abuse potential due to sustained expression of DAT-mediated abuse-related effects and tolerance to SERT-mediated abuse-limiting effects.

Cited by 19 publications

References 48 publications

Designer drugs: mechanism of action and adverse effects

Designer drugs: mechanism of action and adverse effects

Determinants of opioid abuse potential: Insights using intracranial self-stimulation

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

Contact Info

Product

Resources

About