Rewarding and reinforcing effects of 4-chloro-2,5-dimethoxyamphetamine and AH-7921 in rodents

Abstract New psychoactive substances (NPSs), i.e., newly designed substances with chemical residues that are slightly different from those of known psychoactive substances, have been emerging since the late 2000s, and social problems related to the use of these substances are increasing globally. Two such NPSs are 4-chloro-2,5-dimethoxyamphetamine (DOC), a psychedelic substance that is structurally related to amphetamine, and AH-7921, an opioid analgesic that is used for recreational purposes and has a potency similar to that of morphine. Currently, scientific evidence for the dependence liability or toxicity of NPSs is lacking. Therefore, in this study, we performed animal behavioral tests to evaluate the dependence liability of DOC and AH-7921. The rewarding and reinforcing effects of DOC and AH-7921 were evaluated using the conditioned place preference (CPP) paradigm in mice and the self-administration (SA) procedure in rats. Both DOC and AH-7921 increased the preference for the drug-paired compartment in the CPP test at a dose of 0.3 mg/kg and increased the number of responses to the active lever in the SA test at 0.01 mg/(kg·infusion). Collectively, the data suggest that DOC and AH-7921 may have both rewarding and reinforcing effects. Further studies are needed to confirm the reinforcing effects in broader dose ranges with various schedules.