Intravenous self-injection of four novel phenethylamines in baboons

The present study evaluated the intravenous self-administration of four substituted phenethylamines, using a substitution procedure in baboons. Baboons were trained to self-inject 0.32 mg/kg/injection cocaine under a fixed-ratio (FR) schedule, with a 3 h timeout following each injection. Doses of(±)-N-ethyl-3,4-methylenedioxyamphetamine HCl (MDE), (±)-N-hydroxy-3,4-methylenedioxyamphetamine HCl (N-OH-MDA), (+)-N-N-dimethylamphetamine HCl (NNDMA), and 4-bromo-2,5-dimethyoxy-β-phenethylamine (BDMPEA) and their vehicles were substituted for cocaine for 15 or more successive days. High doses of MDE and N-OH-MDA maintained self-injection; however, NNMA and BDMPEA self-injection was less consistent. NNDMA did not reliably maintain self-injection, whereas one or more doses of BDMPEA maintained self-injection in each of three baboons. Intermediate to high doses of all four compounds decreased food pellet intake maintained under a FR schedule of reinforcement on a different fever. In some baboons, high doses of N-OH-MDA, NNDMA and BDMPEA produced signs of behavioral toxicity (e.g. cyclic pattern of self-injection, behavioral agitation, stereotypical movements) that were similar to those previously observed after administration of high doses of classic psychomotor stimulants such as d-amphetamine; however, the severity and profile of this behavioral toxicity differed between compounds. Thus, the present study documents both similarities and differences in the behavioral profiles of these four phenethylamines.