N-benzylpiperazine has characteristics of a drug of abuse

Brennan, Katharine A.; Lake, Barbara; Hely, Lincoln S.; Jones, Karen L.; Gittings, David; Colussi-Mas, Joyce; Fitzmaurice, Paul S.; Lea, Rodney Arthur; Schenk, Susan

doi:10.1097/fbp.0b013e3282f18d8f

Cited by 15 publications

(20 citation statements)

References 40 publications

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“…This elevation results from effects on the release and re‐uptake of both transmitters (Monteiro et al, 2013) via actions on their respective transporters (DATs and SERTs, Baumann et al, 2004) which are major targets of many psychostimulants (Zahniser and Sorkin, 2009). Therefore, contrary to earlier claims, this would make the drug not that different from methamphetamine, a conclusion supported by both behavioral and neurochemical findings (Baumann et al, 2004; Brennan et al, 2007a, b; Herbert and Hughes, 2009; Johnson and Hughes, 2013).…”

Section: Introductioncontrasting

confidence: 78%

Treatment with 1‐benzylpiperazine (BZP) during adolescence of male and female hooded rats exposed to environmental enrichment: Subsequent behavioral outcomes

Dixon

Hughes²

2018

Intl J of Devlp Neuroscience

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From 30 days after birth until the completion of the study, male and female rats were caged in same‐sexed twos or threes either with (enriched cages, EC) or without several objects for them to explore (standard cages, SC). From 41 to 50 days of age (late adolescence), they received a daily intraperitoneal injection of saline, or 10 or 20 mg/kg of the monoaminergic agonist drug of abuse, 1‐benzylpiperazine (BZP). Ten days later (PND60+), their behavior was observed over several days in an open field, an elevated plus maze, a light‐dark box and (to assess short‐term memory) a Y maze in which one of the arms had been changed in brightness between two trials. These tests were repeated from 40 days after PND60+, namely PND100+. While open‐arm occupancy at PND100+ in the plus maze was lower following both doses of the drug for SC rats only, other examples of BZP‐related heightened anxiety were confined to EC rats. This suggested that enrichment had enhanced rather than reduced any anxiogenic effects of the drug treatment. There was no plausible evidence of BZP‐associated impaired spatial memory required to recognize the changed novel Y‐maze arm. Instead, changes in novelty preferences or neophobia‐related anxiety were most likely. While there were also some examples of sex and age differences in the later effects of BZP, in most cases these were evident at both ages following treatment with both BZP doses. A number of overall BZP, cage, sex and age differences, independent of enrichment effects, were also observed.

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Section: Introductioncontrasting

confidence: 78%

Treatment with 1‐benzylpiperazine (BZP) during adolescence of male and female hooded rats exposed to environmental enrichment: Subsequent behavioral outcomes

Dixon

Hughes²

2018

Intl J of Devlp Neuroscience

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“…When combining BZP (0.01 or 0.03 mg/kg/infusion) and TFMPP (0.01, 0.03, or 0.1 mg/kg/infusion), self-administration rates decreased in a TFMPP dose-dependent manner and were lower compared to BZP alone, suggesting that TFMPP attenuated the reinforcing effects of BZP. In a separate study using rats (Brennan et al, 2007), separate groups were initially trained to intravenously self-administer either cocaine or BZP in 2-hr daily access sessions and an FR1 schedule. In cocaine trained rats (0.5 mg/kg/infusion), BZP at doses of 0.125, 0.25 and 0.5 mg/kg/infusion maintained and increased self-administration, but responding extinguished when saline was substituted.…”

Section: Piperazinesmentioning

confidence: 99%

Abuse liability of novel ‘legal high’ designer stimulants

Watterson

2013

Behavioural Pharmacology

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In the last few years, the variety and recreational use of 'legal high' designer stimulants has increased to unprecedented levels. Since their rapid emergence in drug markets, numerous adverse physical and psychological effects have been extensively reported. However, less is understood about the potential for compulsive use of and addiction to these drugs. Recently, a small collection of scientific studies assessing the abuse liability of these drugs has emerged. This new knowledge has been derived primarily from animal studies using behaviorally based procedures which include intravenous self-administration, conditioned place preference, intracranial self-stimulation, and drug discrimination. In this review we present a brief history of the recent rise in designer stimulant use followed by a short methodological description of the aforementioned procedures. We then review neurochemical and abuse liability studies on designer stimulants that have been examined to date. Finally, we conclude with a discussion of these collective findings, our current understanding of the abuse liability of these drugs in relation to each other and the illicit drugs they are designed to mimic, and recommend future research directions.

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“…In invertebrates, changes in movement are the most common endpoints for determining behavioral effects after toxic exposures (Anderson, Cole, & Williams, 2004). In rats, BZP increased locomotor activity (Brennan et al, 2007;Yarosh et al, 2007), enhanced the acquisition and consolidation of memory and presented an anxiogenic profile (Castillo-Hernández et al, 2017), acting selectively at DAT and releasing dopamine (Simmler, Rickli, Schramm, Hoener, & Liechti, 2014). In C. elegans, when neuronal functions are impaired, changes in behavior may appear (Fagundez et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans

Souto

Göethel

Peruzzi

et al. 2019

J of Applied Toxicology

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Piperazine designer drugs are a group of synthetic drugs of abuse that have appeared on the illicit market since the second half of the 1990s. The most common derivatives are 1‐benzylpiperazine (BZP), 1‐(4‐methoxyphenyl)piperazine (MeOPP) and 1‐(3,4‐methylenedioxybenzyl)piperazine (MDBP). They can be consumed as capsules, tablets, but also in powder or liquid forms. Generally, although less potent than amphetamines, piperazines have dopaminergic and serotonergic activities. The aim of this work was to evaluate the toxic effects of BZP, MeOPP and MDBP using Caenorhabditis elegans as in vivo model for acute toxicity, development, reproduction and behavior testing. The LC50 for BZP, MeOPP and MDBP were 52.21, 5.72 and 1.22 mm, respectively. All concentrations induced a significant decrease in the body surface of the worms, indicating developmental alterations, and decrease in the brood size. Worms exposed to piperazine designer drugs also presented a decrease in locomotor activity and mechanical sensitivity, suggesting the possible dysfunction of the nervous system. Neuronal damage was confirmed through the decrease in fluorescence of BY200 strains, indicating loss of dopaminergic transporters. In conclusion, we suggest that piperazine designer drugs lead to neuronal damage, which might be the underlying cause of the altered behavior observed in humans.

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N-benzylpiperazine has characteristics of a drug of abuse

Cited by 15 publications

References 40 publications

Treatment with 1‐benzylpiperazine (BZP) during adolescence of male and female hooded rats exposed to environmental enrichment: Subsequent behavioral outcomes

Treatment with 1‐benzylpiperazine (BZP) during adolescence of male and female hooded rats exposed to environmental enrichment: Subsequent behavioral outcomes

Abuse liability of novel ‘legal high’ designer stimulants

Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans

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