Synthetic cathinones share potent sympathomimetic properties with amphetamines due to their shared phenethylamine backbone. Despite recent work focused on understanding the behavioral effects of synthetic cathinones, a systematic comparison of neuropharmacology, behavior, and physiological effects with other stimulants, has remained elusive. In the present study, we explore the behavioral effects of cathinones in crayfish, a model system which combines a well characterized behavioral paradigm for addiction-like behaviors, a modularly organized nervous system, the lack of a formal blood-brain barrier, and experimental tractability. The objective of this study was to characterize the psychomotor and rewarding effects of methylated cathinones (methylone, mephedrone), and their non β-ketone substituted amphetamine analogs (4-methylmethamphetamine, 4-MMA and 3,4-methylenedioxymethamphetamine MDMA) in crayfish. Our results suggest that these drugs produce psychostimulation, which sensitizes upon repeated drug administration. Furthermore, crayfish demonstrated a conditioned substrate preference for mephedrone and 4-MMA drug-pairings at a 10 μg/g dose, a preference which persisted even through a series of extinction trials. Our study indicates that synthetic cathinones and substituted amphetamine analogues produce distinct behavioral effects in an invertebrate system which consists of a relatively simple neuronal organization. The present findings provide an evolutionary context to our understanding about how drugs of abuse initiate reward at levels far beyond those specific to humans.
Keywords: Addiction; Conditioned place preference (CPP); Crayfish; Invertebrate reward; Phenethylamines; Psychostimulant sensitization.
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