5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride (Foxy)-induced cognitive deficits in rat after exposure in adolescence

Compton, David M.; Dietrich, Kerri L.; Selinger, Melissa C.; Testa, Erin K.

doi:10.1016/j.physbeh.2011.01.021

Cited by 18 publications

(26 citation statements)

References 46 publications

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“…In previous research (Compton et al, 2011), we failed to find an effect of adolescent exposure period (mid vs. late adolescence) in a number of spatial tasks in the MWM. On MWM tasks that required the flexible use of multiple spatial cues, the performance of the rats exposed to 5-MeO-DIPT during adolescence was inferior to that of salinetreated rats.…”

Section: Discussioncontrasting

confidence: 62%

“…Among other things, adolescence in humans is associated with high levels of sensation-seeking behavior and a desire for novelty (Adriani & Laviola, 2004). However, in addition to the reported learning, memory, impulsivity, and cognitive impairments described here and elsewhere (e.g., Compton et al, 2011;Green et al, 2003;Skelton et al, 2006Skelton et al, , 2009) the use of these drugs appears to carry a number of inherent risks. For example, among the reported long-term consequences associated with the use of MDMA are nonmemorial (e.g., Parkinson's Disease; Morton, 2005) deficits.…”

Section: Discussionmentioning

confidence: 66%

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Differentiation of MDMA or 5-MeO-DIPT induced cognitive deficits in rat following adolescent exposure.

Compton¹,

Selinger²,

Westman³

et al. 2011

Psychology & Neuroscience

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The so-called "club drug" Foxy or Methoxy Foxy (5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride; 5-MeO-DIPT) is a newer drug of abuse that has recently gained in popularity among recreational users as an alternative to MDMA (Ecstasy). While considerable research into the consequences of MDMA use is available, much remains unknown about the neurobiological consequences of 5-MeO-DIPT use. In the present study, beginning at 35 days of age adolescent rats were given repeated injections of 10 mg/kg of 5-MeO-DIPT, MDMA, or a corresponding volume of isotonic saline. Adult animals (135 days old) were trained and tested on a number of tasks designed to assess the impact, if any, and severity of 5-MeO-DIPT and MDMA, on a series of spatial and nonspatial memory tasks. Both the 5-MeO-DIPT-and the MDMA-treated rats were able to master the spatial navigation tests where the task included a single goal location and all groups performed comparably on these phases of training and testing. Conversely, the performance of both groups of the drug-treated rats was markedly inferior to that of the control animals on a task where the goal was moved to a new location and on a response learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. In addition, in a response learning version of a learning set task, 5-MeO-DIPT rats made significantly more working memory errors than MDMA or control rats. Results are discussed in terms of observed alterations in serotonin activity in the forebrain and the consequences of compromised serotoninergic systems on cognitive processes.

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Section: Discussioncontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 66%

Differentiation of MDMA or 5-MeO-DIPT induced cognitive deficits in rat following adolescent exposure.

Compton¹,

Selinger²,

Westman³

et al. 2011

Psychology & Neuroscience

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“…As Nyberg [15] noted, a number of cognitive processes-contextual memory, spatial memory, and working memory-are directly regulated or influenced by adult hippocampal neurogenesis (see also, [117] To reiterate, much less is known about the effects of Foxy [26]. Foxy has effects on 5-HT systems in the brain, acting on the 5-HT2A receptor [123] as a SERT inhibitor [124].…”

Section: Discussionmentioning

confidence: 99%

“…Research into the effects of Foxy with rodent models have led to reports of Foxy-associated deficits [24] [25] [26] [27]. While the specific effects associated with exposure to Foxy remains to be elucidated, the available evidence is suggestive of deficits primarily associated with compromised attentional processes and [28].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Examination of Learning and Memory in Rats Following Adolescent Exposure to 3,4-Methylenedioxymethamphetamine or 5-Methoxy-N,N-Diisopropyltryptamine

Compton¹,

Dietrich²,

Esquivel³

2017

JBBS

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A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown about the neurobiological consequences of Foxy use. In addition, research into the long-term neuropsychological repercussions associated with these two compounds remains incomplete. The goal of the present research was to explore the effects of MDMA or Foxy on cognitive processes associated with adolescent exposure considered over much of the lifespan. Here we investigated whether the reported effects following adolescent exposure resolved in early adulthood or continued throughout life. The protocol involved repeated doses of either MDMA or Foxy during the period defined as mid-adolescence (postnatal days 34 -46) in rats, followed by the use of four series of learning and memory tasks repeated at different points in the rodent lifespan. At four time points in adulthood, the animals were trained and tested on a on a series of spatial and nonspatial memory tasks designed to assess the impact and severity of Foxy and MDMA. Oddly, MDMA-treated rats were impaired on a step down passive avoidance task. The performance of the drug-treated rats was markedly inferior to that of the control animals on more demanding water maze tasks, with some results suggesting a lack of flexibility in adapting to changing task demands. MDMA rats were the most impaired. While some persistent cognitive deficits were found, no significant group differences in serotonin or dopamine levels were found in any of the measured regions of the brain changes, cortical or subcortical. These results provide evidence for compromised neurocognition that continues long after drug exposure in the How to cite this paper:

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“…High concentrations of 5-MeO-DIPT produced a marked cytotoxicity assessed by a cell viability assay in COS-7 cells [3]. Chronic 5-MeO-DIPT administration decreased 5-HT levels in the rat prefrontal cortex, striatum and hippocampus [7][8][9], which may suggest its neurotoxicity. Clinical data indicated potent multi-organ effects of 5-MeO-DIPT as the users experienced euphoria, disinhibition, increased sociability, and visual and auditory hallucinations, but also effects like mioclonus, restlessness, insomnia, anxiety, nausea, vomiting and diarrhea [10].…”

Section: Introductionmentioning

confidence: 98%

Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats

et al. 2018

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Purpose Tryptamine hallucinogen 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a serotonin transporter inhibitor with high affinity for serotonin 5-HT 1A and 5-HT 2A/C receptors. We showed previously that 5-MeO-DIPT in a single dose increased neurotransmitter release in brain regions of rats and elicited single-and double-strand DNA breaks. Herein we investigated the effects of repeated-intermittent 5-MeO-DIPT administration in adolescence on dopamine (DA), serotonin (5-HT) and glutamate release in brain regions of adult rats. Furthermore, we examined caspase-3 activity, oxidative DNA damage, the Gpx3, Sod1, Ht1a and Ht2a mRNA expression levels, and cell viability. Methods Neurotransmitter release was measured by microdialysis in freely moving animals. Caspase-3 activity was assessed colorimetrically, and oxidative DNA damage with the comet assay, while the Gpx3, Sod1, Ht1a and Ht2a mRNA expression levels were assessed by real-time polymerase chain reaction. Cell viability was studied in SH-SY5Y and Hep G2 cells by the MTT test. Results We observed changed responses of DA, 5-HT and glutamate neurons to a challenge dose of 5-MeO-DIPT when animals were treated repeatedly in adolescence with this hallucinogen. The basal extracellular levels of DA and 5-HT were decreased in the striatum and nucleus accumbens, while glutamate level was increased in the nucleus accumbens and frontal cortex. The damage of cortical DNA, increased Gpx3 and Sod1 mRNA expression and affected caspase-3 activity were also observed. Furthermore, decreased Ht1a and Ht2a mRNA expression in the frontal cortex and marked cytotoxicity of 5-MeO-DIPT were found. Conclusions These results suggest that 5-MeO-DIPT given repeatedly during adolescence affects brain neurotransmission and shows neurotoxic potential observed in adult animals.

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5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride (Foxy)-induced cognitive deficits in rat after exposure in adolescence

Cited by 18 publications

References 46 publications

Differentiation of MDMA or 5-MeO-DIPT induced cognitive deficits in rat following adolescent exposure.

Differentiation of MDMA or 5-MeO-DIPT induced cognitive deficits in rat following adolescent exposure.

Longitudinal Examination of Learning and Memory in Rats Following Adolescent Exposure to 3,4-Methylenedioxymethamphetamine or 5-Methoxy-N,N-Diisopropyltryptamine

Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats

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