Two newly-emerging substituted phenethylamines MAL and BOD induce differential psychopharmacological effects in rodents

The substituted phenethylamines MAL and BOD have different abuse potentials. MAL produced psychostimulant effects, locomotor sensitization, and was self-administered by rats, indicating reinforcing properties. Both drugs induced conditioned place preference in mice, which was blocked by dopamine receptor antagonists, and both altered dopamine receptor D1 and D2 protein expression in the nucleus accumbens, tyrosine hydroxylase and dopamine transporter in the ventral tegmental area, increased dopamine levels in the nucleus accumbens, and enhanced delta and gamma brain wave activity. BOD caused locomotor depression and lacked rewarding and reinforcing effects, suggesting little to no capability to engender compulsive behavior despite its dopaminergic alterations.

Study at a glance

Abstract

Background: Recently, the recreational use of substituted phenethylamines has grown rapidly. Among these are 2-(3,5-dimethoxy-4-((2-methylallyl)oxy)phenyl)ethanamine (MAL) and 2-(2,5-dimethoxy-4-methylphenyl)-2-methoxyethan-1-amine (BOD). However, studies characterizing their abuse potential are still lacking. Aim: The purpose of this study was to investigate the abuse potential of MAL and BOD. Methods: The psychostimulant, reinforcing, and rewarding properties of MAL and BOD were analyzed using locomotor sensitization, self-administration, and conditioned place preference tests. Dopamine antagonists (i.e. SCH23390, haloperidol) were administered during conditioned place preference to evaluate the involvement of the mesolimbic dopamine system. Furthermore, dopamine-related protein expression in the nucleus accumbens and the ventral tegmental area was measured along with dopamine concentrations in the nucleus accumbens. Electroencephalography was conducted to determine effects of MAL and BOD on brain wave activity. Results: MAL induced psychostimulant effects and sensitization, while BOD induced locomotor depression in mice. Only MAL was self-administered by rats. Both drugs induced conditioned place preference in mice at different doses; dopamine receptor antagonists blocked MAL- and BOD-induced conditioned place preference. Both the compounds altered the expression of dopamine receptor D 1 and D 2 proteins in the nucleus accumbens and tyrosine hydroxylase (TH) and dopamine transporter in the ventral tegmental area, enhanced dopamine levels in the nucleus accumbens, and increased delta and gamma wave activities in the brain. Conclusions: MAL may induce abuse potential via the mesolimbic dopaminergic system and possibly accompanied by alterations in brain wave activity. Moreover, the lack of rewarding and reinforcing effects in BOD suggest that this drug may have little to no capability to engender compulsive behavior, though having found to induce alterations in dopaminergic system and brain wave activities.