The drugs 2C-C and 2C-P, members of the 2C family of phenethylamines, show abuse potential and neurotoxic effects at high doses in animal models. In mice, both drugs produced conditioned place preference in a dose-dependent manner and increased self-administration in rats, indicating abuse potential. High doses decreased locomotor activity, rota-rod performance, and scores on memory tests (Y-maze, novel object recognition, passive avoidance). The drugs altered expression of D1 and D2 dopamine receptors, the dopamine transporter, and its phosphorylated form in the nucleus accumbens and medial prefrontal cortex, and increased c-Fos-positive cells in the nucleus accumbens. High doses also activated microglia, suggesting neuroinflammation in the striatum.
25E-NBOMe, a novel psychoactive substance, induces conditioned place preference in male mice and self-administration in male rats, indicating abuse potential. The drug enhances dopamine transporter and dopamine D1 receptor expression in the nucleus accumbens, reduces dopamine levels, and activates intracellular signaling pathways. Blocking the D1 receptor or inhibiting D1 receptor-expressing neurons attenuates the conditioned place preference. The drug also produces hallucinogenic effects via serotonin 2A receptor activity, as shown by the head twitch response. These findings suggest that D1 receptor signaling may govern the addictive potential of 25E-NBOMe.
Methoxphenidine, a dissociative designer drug, produces addictive behaviors in rats and mice through reinforcing and rewarding effects, activating dopamine pathways in the nucleus accumbens. It also induces schizophrenia-related symptoms—positive (hyperactivity, impulsivity), negative (anxiety, social withdrawal, depression), and cognitive impairment—by disrupting the hippocampal-prefrontal cortex pathway, a circuit implicated in schizophrenia. These findings support legal restrictions on recreational use and suggest methoxphenidine may serve as a tool for developing animal models of addiction and schizophrenia.