Detrimental effects of the ‘bath salt’ methylenedioxypyrovalerone on social play behavior in male rats

Abstract

Methylenedioxypyrovalerone (MDPV) is the most popular synthetic cathinone found in products marketed as 'bath salts', widely abused among teenagers and young adults. Synthetic cathinones have pharmacological effects resembling those of psychostimulants, which are known to disrupt a variety of social behaviors. However, despite the popular use of MDPV by young people in social contexts, information about its effects on social behavior is scarce. To investigate the impact of MDPV on social behavior at young age, and the underlying neurobehavioral mechanisms, we focused on social play behavior. Social play behavior is the most characteristic social behavior displayed by young mammals and it is crucial for neurobehavioral development. Treatment with MDPV reduced social play behavior in both juvenile and young adult male rats, and its play-suppressant effect was subject to tolerance but not sensitization. As the behavioral effects of MDPV have been ascribed to dopaminergic and noradrenergic neurotransmission, and given the role of these neurotransmitters in social play, we investigated the involvement of dopamine and noradrenaline in the play-suppressant effects of MDPV. The effects of MDPV on social play were blocked by either the α2 adrenoceptor antagonist RX821002 or the dopamine receptor antagonist flupenthixol, given alone or together at subeffective doses. In sum, MDPV selectively suppresses the most vigorous social behavior of developing rats through both noradrenergic and dopaminergic mechanisms. This study provides important preclinical evidence of the deleterious effects of MDPV on social behavior, and as such increases our understanding of the neurobehavioral effects of this popular cathinone.

Sex and Gender Differences in the Effects of Novel Psychoactive Substances

“…Notably, the second generation cathinones pentylone and pentedrone were reported to possess greater abuse liability than first generation cathinone 3,4-methylenedioxymethcathinone (methylone) [ 112 ]. Synthetic cathinones were reported to also affect spontaneous and stimulated motor responses [ 110 , 113 ], exert a negative impact on cognitive [ 114 ] and memory processes [ 115 ] and suppress social behavior in both juvenile and young adult animals [ 116 ]. These NPS are frequently used in association with other drugs of abuse, polyconsumption typically resulting in the potentiation of their negative effects [ 117 ].…”

Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review

“…injections can cause interoceptive dose-time dependent effects [ 47 ] and increase mice motility 30 min after the first injection [ 48 ]. Methylenedioxypyrovalerone induced self administration in rats [ 49 ] and compromised discrimination between familiar and unfamiliar objects [ 50 ]; it compromised NOR [ 50 , 51 ] and its ingestion caused social play behavior repression in rats [ 52 ]. Treatment with α-PVT can induce self administration in rats [ 53 ] and stimulate locomotion in mice [ 54 ].…”

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

“…Moreover, it led to the reduction of social play behavior in young adult male rats, while effects were blocked by RX821002 and flupenthixol, respectively, α 2 and dopamine receptor antagonists [ 142 ]. Drug-induced dopaminergic activity parallels the locomotor stimulation and rewarding effect [ 118 , 143 , 144 ]. Methylone is a nonspecific substrate [ 118 ], producing an inward current at SERT but not at DAT, similarly to MDMA [ 145 ], and oxidative stress, which is responsible for the neurotoxicity of methylone and, to a greater extent, MDPV [ 146 ].…”