Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

Abstract

The drastic increase in hallucinogenic compounds in illicit drug markets of new psychoactive substances (NPS) is a worldwide threat. Among these, 2, 5-dimetoxy-4-bromo-amphetamine (DOB) and paramethoxyamphetamine (PMA; marketed as “ecstasy”) are frequently purchased on the dark web and consumed for recreational purposes during rave/dance parties. In fact, these two substances seem to induce the same effects as MDMA, which could be due to their structural similarities. According to users, DOB and PMA share the same euphoric effects: increasing of the mental state, increasing sociability and empathy. Users also experienced loss of memory, temporal distortion, and paranoia following the repetition of the same thought. The aim of this study was to investigate the effect of the acute systemic administration of DOB and PMA (0.01–30 mg/kg; i.p.) on motor, sensorimotor (visual, acoustic, and tactile), and startle/PPI responses in CD-1 male mice. Moreover, the pro-psychedelic effect of DOB (0.075–2 mg/kg) and PMA (0.0005–0.5 mg/kg) was investigated by using zebrafish as a model. DOB and PMA administration affected spontaneous locomotion and impaired behaviors and startle/PPI responses in mice. In addition, the two compounds promoted hallucinatory states in zebrafish by reducing the hallucinatory score and swimming activity in hallucinogen-like states.

Effect of -NBOMe Compounds on Sensorimotor, Motor, and Prepulse Inhibition Responses in Mice in Comparison With the 2C Analogs and Lysergic Acid Diethylamide: From Preclinical Evidence to Forensic Implication in Driving Under the Influence of Drugs

“…This time, from the comparison graphs of the maximum and average effects of all tested compounds, it is clear that 25I-NBOMe has a higher inhibitory effect ( Figures 4H,I ). Results are in accordance with previous studies conducted with other hallucinogenic substances, such as DOI ( 50 ) and 25I-NBOMe ( 37 ) on rats, Dimethoxybromoamphetamine (DOB), and Paramethoxyamphetamine (PMA) on mice ( 38 ). Evidence accumulated over the past 5 decades has indicated that the behavioral effects of hallucinogenic compounds are mediated by interactions with serotonin receptors in the brain ( 10 , 15 , 32 , 51 , 52 ), resulting in exceptionally strong behavioral and psychoactive properties in animals and humans ( 12 , 34 , 53 , 54 ).…”

“…The effects of 25H-NBOMe, 25I-NBOMe, 25B-NBOMe, 2C-H, 2C-I, 2C-B, and LSD were investigated using a consolidated battery of behavioral tests routinely used in our laboratory for preclinical investigation of NPSs in rodents ( 38 , 42 , 43 ).…”

Worsening of the Toxic Effects of (±)Cis-4,4′-DMAR Following Its Co-Administration with (±)Trans-4,4′-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice

“…The effects of (±)cis-4,4 -DMAR, (±)trans-4,4 -DMAR and their co-administration were investigated by a protocol widely used in studies of "safety pharmacology" for the preclinical characterization of new molecules in rodents [106][107][108][109]. This protocol includes a series of observational behavioural tests carried out in a consecutive manner that monitor the animal responses up to 5 h after compound injections.…”

In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP

“…In fact, tramadol, by increasing 5-HT levels, may induce visual alterations via the activation of serotonin receptors in the cortico-visual circuits [ 30 , 31 ]. In particular, the inhibition of both visual object and visual placing responses in rodents has been observed after the systemic administration of MDMA [ 32 ], DOB [ 33 ] or the potent serotoninergic agonist 25I-NBOMe [ 34 ].…”

“…Therefore, this motor inhibition could possibly be due to either an anxiogenic effect of the molecule (stimulation of the noradrenergic fight-or-flight response) or as a consequence of the impaired visual and acoustic sensorimotor responses. In fact, the systemic administration of hallucinogenic phenethylamines that act as 5-HT receptor agonists, such as DOB, 2C-I and 25I-NBOMe [ 43 ], profoundly inhibits visual and acoustic sensorimotor responses in CD-1 mice, inducing a mild inhibition of spontaneous locomotion [ 33 ].…”