Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: Evidence of its abuse potential

Botanas, Chrislean Jun; Peña, June Bryan de la; Peña, Irene Joy dela; Tampus, Reinholdgher; Yoon, Robin; Kim, Hee Jin; Lee, Yong Sup; Jang, Choon‐Gon; Cheong, Jae Hoon

doi:10.1016/j.pbb.2015.03.007

Cited by 59 publications

(48 citation statements)

References 33 publications

(11 reference statements)

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“…In addition, PIPP failed to induce locomotor sensitization, even the highest dose (30 mg/kg) tested did not increase the locomotor of the mice. However, this result is similar to our previous study showing methoxetamine produced CPP albeit its inability to increase the locomotor activity of the rats (Botanas et al ., 2015). Although it did not induce SA or locomotor sensitization, the CPP and qRT-PCR results could not be discounted.…”

Section: Discussionsupporting

confidence: 93%

The Abuse Potential of α-Piperidinopropiophenone (PIPP) and α-Piperidinopentiothiophenone (PIVT), Two New Synthetic Cathinones with Piperidine Ring Substituent

Botanas

Yoon

Peña

et al. 2017

Biomol Ther (Seoul)

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A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) α-piperidinopropiophenone (PIPP) and (2) α-piperidinopentiothiophenone (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.

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Section: Discussionsupporting

confidence: 93%

The Abuse Potential of α-Piperidinopropiophenone (PIPP) and α-Piperidinopentiothiophenone (PIVT), Two New Synthetic Cathinones with Piperidine Ring Substituent

Botanas

Yoon

Peña

et al. 2017

Biomol Ther (Seoul)

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“…Several other preclinical studies have demonstrated that self-administration of ketamine at higher doses, as well as similar drug analogs, can be readily acquired (Botanas et al 2015; Collins and Woods 2007; De Luca and Badiani 2011; Huang et al 2015; van der Kam et al 2007), but these studies utilized daily self-administration paradigms, and they do not include females in their experimental designs. Our results build upon these findings, showing that male and female rats in proestrus will acquire response at FR1, even when self-administering a low dose of ketamine (0.1 mg/kg/infusion) once every fourth day.…”

Section: Discussionmentioning

confidence: 99%

Reinforcing properties of an intermittent, low dose of ketamine in rats: effects of sex and cycle

et al. 2016

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Rationale Repeated intermittent exposure to ketamine has rapid and long-lasting antidepressant effects, but the abuse potential has only been assessed at high doses. Furthermore, while females are more susceptible to depression and more sensitive to ketamine’s antidepressant-like effects, the abuse potential for ketamine in females is unknown. Objectives The objectives of this study are to determine the reinforcing properties of low-dose intermittent ketamine in adult rats of both sexes and determine whether cycling gonadal hormones influence females’ response to ketamine. In male rats, we also aimed to determine whether reinstatement to intermittent ketamine is comparable to intermittent cocaine. Methods Male rats intravenously self-administered cocaine (0.75 mg/kg/infusion) or ketamine (0.1 mg/kg/infusion) once every fourth day, while intact cycling female rats self-administered ketamine only during preidentified stages of their 4-day estrus cycle, when gonadal hormones are either high (proestrus) or low (diestrus). After acquiring self-administration, rats underwent daily extinction training followed by cue-primed and drug-primed reinstatement to assess drug-seeking behavior. Results Diestrus-trained females fail to maintain ketamine self-administration and did not display reinstatement to ketamine-paired cues. Males and proestrus-trained females reinstated to ketamine-paired cues. Ketamine-primed reinstatement was dependent on simultaneous cue presentation. Male rats reinstated to cocaine priming independent of cue presentation. Conclusion These findings indicate that females’s responsivity to this dose of ketamine depends on stage of cycle, as only proestrus-trained females and males respond to ketamine’s reinforcing effects under this treatment paradigm.

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“…It has been shown that methoxetamine increases electrically-stimulated DA release from slices of rat nucleus accumbens and inhibits DA reuptake . Demonstration that methoxetamine produced conditioned place preference and was self-administered by rats, indicates that the drug possesses abuse potential (Botanas et al, 2015). deeper inside the self, spiritual and transcendental experiences, and at high doses out-of-body or even near-death experiences (Corazza et al, 2013;Hofer et al, 2012;Kjellgren and Jonsson, 2013;Zawilska, 2014).…”

Section: Methoxetaminementioning

confidence: 99%

Next generation of novel psychoactive substances on the horizon – A complex problem to face

Zawilska

Andrzejczak

2015

Drug and Alcohol Dependence

162

126

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Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: Evidence of its abuse potential

Cited by 59 publications

References 33 publications

The Abuse Potential of α-Piperidinopropiophenone (PIPP) and α-Piperidinopentiothiophenone (PIVT), Two New Synthetic Cathinones with Piperidine Ring Substituent

The Abuse Potential of α-Piperidinopropiophenone (PIPP) and α-Piperidinopentiothiophenone (PIVT), Two New Synthetic Cathinones with Piperidine Ring Substituent

Reinforcing properties of an intermittent, low dose of ketamine in rats: effects of sex and cycle

Next generation of novel psychoactive substances on the horizon – A complex problem to face

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