Relative reinforcing effects of dibutylone, ethylone, and N-ethylpentylone: self-administration and behavioral economics analysis in rats

Lai, Ming-Kuen; Fu, Dan; Xu, Zehong; Du, Han; Liu, Huifen; Wang, Youmei; Xu, Ping; Zhou, Wenhua

doi:10.1007/s00213-022-06173-x

Cited by 7 publications

(13 citation statements)

References 38 publications

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“…Although work with conditioned place preference (CPP) has been reported with a number of synthetic cathinones (see Cheong et al, 2017; Gannon et al, 2017; Gatch et al, 2015; King, Wakeford, et al, 2015; King, Wetzell, et al, 2015; Marusich et al, 2016; Nelson et al, 2017; Risca et al, 2020), such work has not been assessed with eutylone. However, work with methylone (Karlsson et al, 2014; Miyazawa et al, 2011) has shown its ability to support place preference conditioning and eutylone’s structural isomers induce locomotor activation (Glatfelter et al, 2021; Javadi-Paydar et al, 2018; López-Arnau et al, 2012; Saha et al, 2019), substitute for cocaine and amphetamine (among other drugs of abuse) in drug discrimination assessments (Dolan et al, 2018; Gatch et al, 2019), and support intravenous self-administration (IVSA; Dolan et al, 2018; Javadi-Paydar et al, 2018; Khom et al, 2021; Lai et al, 2022), indicating their abuse potential.…”

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confidence: 99%

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Jones¹,

Huang²,

Manke³

et al. 2023

Experimental and Clinical Psychopharmacology

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Recently, use of the synthetic cathinone (aka "bath salt") eutylone has risen in the United States and globally. Due to its novelty in drug markets, its affective properties remain largely uninvestigated. In this context, drugs of abuse have both rewarding and aversive effects and understanding these effects, their relative balance, and factors that impact each are important to understanding the likelihood of drug use and abuse. This investigation attempted to characterize eutylone's rewarding and aversive effects in a combined conditioned taste avoidance/place preference assay. Female Sprague-Dawley rats were given 20-min access to saccharin, injected with one of five doses of eutylone (0, 3, 10, 18, 32 mg/kg; intraperitoneally; IP), and placed on one side of a place conditioning apparatus. On the following day, subjects were given 20-min access to water, injected IP with vehicle, and placed on the other side of the apparatus. After five conditioning cycles, place preference and saccharin avoidance were assessed. Eutylone induced significant taste avoidance but did not significantly increase time spent on the drug-paired side (relative to controls). Excluding animals with high initial side preference, however, eutylone induced a preference at all doses with the high dose group displaying higher preference than controls. There was no significant correlation between eutylone's aversive and rewarding effects. These data indicate that eutylone (like other synthetic cathinones) induces both rewarding and aversive effects and highlight the need to assess the impact of various factors on its affective properties (and their balance) and on their use and abuse. Public Health SignificanceThis study is the first to demonstrate taste avoidance and place preference induced by the novel synthetic cathinone eutylone. Given that a drug's aversive and rewarding effects are thought in balance to mediate its use and abuse, the present study indicates the potential abuse of eutylone and the importance in assessing various factors that could affect this liability.

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confidence: 99%

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Jones¹,

Huang²,

Manke³

et al. 2023

Experimental and Clinical Psychopharmacology

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“…Likewise, MDPV, i.e., the powerful stimulant structurally similar to 3,4-MDPHP, was shown to be consistently self-administered by rats at rates comparable with or higher than those observed during self-administration of methamphetamine [ 48 , 49 ]. In line with this observation, other substituted phenethylamines and synthetic cathinones, such as methylone, are robustly self-administered by rats [ 50 , 51 , 52 ], although failure to acquire self-administration behavior was recently reported for a newly emerging substituted phenethylamine, i.e., 2-(2,5-dimethoxy-4-methylphenyl)-2-methoxyethan-1-amine (BOD) [ 53 ]. All this evidence supported the hypothesis that 2-Cl-4,5-MDMA and 3,4-MDPHP could also be able to sustain reliable operant behavior in rats.…”

Section: Discussionmentioning

confidence: 91%

Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences

et al. 2022

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The illicit drug market of novel psychoactive substances (NPSs) is expanding, becoming an alarming threat due to increasing intoxication cases and insufficient (if any) knowledge of their effects. Phenethylamine 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) and synthetic cathinone 3,4-methylenedioxy-α-pyrrolidinohexanophenone (3,4-MDPHP) are new, emerging NPSs suggested to be particularly dangerous. This study verified whether these two new drugs (i) possess abuse liability, (ii) alter plasma corticosterone levels, and (iii) interfere with dopaminergic transmission; male and female adolescent rats were included to evaluate potential sex differences in the drug-induced effects. Findings show that the two NPSs are not able to sustain reliable self-administration behavior in rats, with cumulatively earned injections of drugs being not significantly different from cumulatively earned injections of saline in control groups. Yet, at the end of the self-administration training, females (but not males) exhibited higher plasma corticosterone levels after chronic exposure to low levels of 3,4-MDPHP (but not of 2-Cl-4,5-MDMA). Finally, electrophysiological patch-clamp recordings in the rostral ventral tegmental area (rVTA) showed that both drugs are able to increase the firing rate of rVTA dopaminergic neurons in males but not in females, confirming the sex dimorphic effects of these two NPSs. Altogether, this study demonstrates that 3,4-MDPHP and 2-Cl-4,5-MDMA are unlikely to induce dependence in occasional users but can induce other effects at both central and peripheral levels that may significantly differ between males and females.

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“…In the dose–response curve test, one‐way ANOVA was used to compare the difference of mean infusions earned for each dose of drugs across sessions with that in the saline group, followed by the Bonferroni t ‐test for multiple comparisons. Reinforcement potency for each rat was measured by the unit dose that maintained the most responses on the dose–response curve and was indicated as the group mean ± 95% confidence interval as described before 9,10 …”

Section: Methodsmentioning

confidence: 99%

“…The rodent conditioned place preference (CPP) model is one of the most popular drug reward paradigms and has been used widely to detect the rewarding effect of METH 5,6 . Moreover, the intravenous self‐administration model is considered the golden standard for evaluating the drug abuse potential, which has been used to assay not only the reinforcing effect of METH 7 but also the potency 8 and efficacy of METH reinforcement 9–11 …”

Section: Introductionmentioning

confidence: 99%

N‐Isopropylbenzylamine‐induced conditioned place preference, sensitization behaviour and self‐administration in rodents

Lai,

Fu,

et al. 2024

Addiction Biology

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N‐Isopropylbenzylamine (N‐ipb), a chain isomer of methamphetamine (METH) with similar physical properties, has been used as a substitute for METH in seized drug samples. However, the abuse potential of N‐ipb remains unclear. Therefore, this study aimed to evaluate the abuse potential of N‐ipb in comparison to METH, by using conditioned place preference (CPP), locomotor sensitization and intravenous self‐administration tests. The results showed that N‐ipb at a dose of 3 mg·kg−1 significantly induced CPP in mice, which was comparable to the effect of METH at 1 mg·kg−1. Either acute or repeated N‐ipb injections (1 or 3 mg·kg−1) failed to raise the locomotor activity. However, acute treatment with 10 mg·kg−1 N‐ipb elevated the locomotor activity compared with saline, while chronic injection of 10 mg·kg−1 N‐ipb induced a delayed and attenuated sensitization compared with 1 mg·kg−1 METH. Rats could acquire N‐ipb self‐administration at a dose of 1 mg·kg−1·infusion−1, and a typical inverted U‐shaped dose–response curve was obtained for N‐ipb. The mean dose of N‐ipb that maintained the maximum response was greater than that of METH, indicating that N‐ipb is less potent for reinforcement than METH. In the economic behavioural analysis, comparison of essential values derived from the demand elasticity revealed that N‐ipb is less efficacy as a reinforcer than METH. The present data demonstrate that N‐ipb functions as a reinforcer and has a potential for abuse. However, the potency of psychomotor stimulation and the reinforcing effectiveness of N‐ipb are lower than those of METH.

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Relative reinforcing effects of dibutylone, ethylone, and N-ethylpentylone: self-administration and behavioral economics analysis in rats

Cited by 7 publications

References 38 publications

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences

N‐Isopropylbenzylamine‐induced conditioned place preference, sensitization behaviour and self‐administration in rodents

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