Locomotor stimulant and discriminative stimulus effects of ‘bath salt’ cathinones

Gatch, Michael B.; Taylor, Craig; Forster, Michael J.

doi:10.1097/fbp.0b013e328364166d

Cited by 158 publications

(201 citation statements)

References 16 publications

(45 reference statements)

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“…In addition to its prolonged effects on blocking DAT-mediated transport, MDPV is also a potent norepinephrine transporter (NET) inhibitor, with greater potency for NET than cocaine or METH (Simmler et al, 2013). Consistent with its potent activity at striatal DATs and NETs, MDPV is also a potent locomotor stimulant (Gatch et al, 2013) and produces conditioned place preference in both rats and mice (Karlsson et al, 2014;King et al, 2015). It also significantly elevates extracellular levels of dopamine in the striatum (Baumann et al, 2012).…”

Section: Discussionmentioning

confidence: 91%

“…Animal studies (Aarde et al, 2013;Baumann et al, 2012;Bonano et al, 2014;Gatch et al, 2013;Huang et al, 2012;Marusich et al, 2014b;Watterson et al, 2014) and in vitro monoamine transporter assays (Baumann et al, 2012) have shown that MDPV produces typical psychostimulant-like effects, with a mechanism of action that is similar to and, yet, more powerful and longer lasting than cocaine. The biological activity of bath salts, including MDPV, is thought to be largely mediated through their effects on mesostriatal monoaminergic neurotransmission (Cozzi et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

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The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Colon-Perez

Tran

Thompson

et al. 2016

Neuropsychopharmacol

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The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D 1 /D 2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Colon-Perez

Tran

Thompson

et al. 2016

Neuropsychopharmacol

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“…Although the synthetic cathinone compounds MDPV and mephedrone are less well studied than MA, these compounds can stimulate motor activity in mice (Fantegrossi et al, 2013;Fuwa et al, 2009;Gatch et al, 2013) and rats Baumann et al, 2012Baumann et al, , 2013Huang et al, 2012;Wright et al, 2012) when administered by injection. MDPV appears to be approximately as potent as MA whereas mephedrone is less potent in most prior studies, and thus the relative potencies identified for vapor inhalation in this study (a threshold for effects at 12.5-25 mg/ml for MA and MDPV vs above 100 mg/ml for mephedrone, and significant differences in experiment 3 between mephedrone and the other two drugs) are roughly consistent with prior results using other routes of administration.…”

Section: Discussionmentioning

confidence: 99%

Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology

Nguyen

Aarde

Cole

et al. 2016

Neuropsychopharmacol

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Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine.

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“…Users have reported bath salts producing similar subjective effects as known stimulant drugs of abuse, and the clinical presentation is also similar to cocaine and amphetamine-like drugs (Prosser and Nelson, 2012). Our laboratory has previously demonstrated that a number of synthetic cathinones produce locomotor stimulation in mice and cocaine-and methamphetamine-like discriminative stimulus effects in rats (Gatch et al, 2013(Gatch et al, , 2015. The pharmacodynamic profile of synthetic cathinones is also similar to other psychomotor stimulants, with some derivatives producing amphetamine-like monoaminereleasing properties, and others producing cocaine-like blockade of monoamine uptake (Eshleman et al, 2013;Simmler et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Comparative Behavioral Pharmacology of Three Pyrrolidine-Containing Synthetic Cathinone Derivatives

Gatch

Dolan

Forster

2015

J Pharmacol Exp Ther

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Synthetic cathinones, often sold as "bath salts," are a popular class of recreational drugs used as quasi-legal alternatives to cocaine, methamphetamine, and methylenedioxymethamphetamine. The increased prevalence and health consequences of synthetic cathinone use has prompted regulatory agencies to control a number of these compounds; however, a broad class of analogous compounds known as the second-generation cathinones has been brought to the market to take the place of the banned synthetic cathinone derivatives. The current study aims to characterize the behavioral pharmacology of three pyrrolidinylated secondgeneration cathinones: 4-methyl-a-pyrrolidinopropiophenone (4ʹ-MePPP), a-pyrrolidinopropiobutiophenone (a-PBP), and a-pyrrolidinopentiophenone (a-PVP). Locomotor activity was tested in mice over an 8-hour period. The discriminative stimulus effects of these compounds were tested in rats trained to discriminate either cocaine or methamphetamine. The rewarding effects of these drugs were assessed in mice using conditioned place preference. Both a-PBP and a-PVP produced long-lasting increases in locomotor activity across a wide range of doses, whereas 4ʹ-MePPP produced locomotor stimulation only at 30 mg/kg. Both a-PBP and a-PVP fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine, whereas 4ʹ-MePPP substituted fully for the discriminative stimulus effects of methamphetamine only. Both a-PBP and a-PVP produced conditioned place preference in an inverted U-shaped dose effect, whereas 4ʹ-MePPP did not produce conditioned place preference. These findings suggest that a-PBP and a-PVP are likely to be recreationally used and have potential for addiction and abuse, but 4ʹ-MePPP may not.

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Locomotor stimulant and discriminative stimulus effects of ‘bath salt’ cathinones

Cited by 158 publications

References 16 publications

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology

Comparative Behavioral Pharmacology of Three Pyrrolidine-Containing Synthetic Cathinone Derivatives

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