Intravenous self-injection of four novel phenethylamines in baboons

Intravenous self-administration of four substituted phenethylamines was evaluated in baboons trained to self-inject cocaine. High doses of MDE and N-OH-MDA maintained self-injection, while NNDMA did not reliably do so, and BDMPEA maintained self-injection in each of three baboons at one or more doses. Intermediate to high doses of all four compounds decreased food pellet intake. In some baboons, high doses of N-OH-MDA, NNDMA, and BDMPEA produced signs of behavioral toxicity similar to those of classic psychomotor stimulants, though severity and profile differed between compounds. The study documents both similarities and differences in the behavioral profiles of these phenethylamines.

Study at a glance

Abstract

The present study evaluated the intravenous self-administration of four substituted phenethylamines, using a substitution procedure in baboons. Baboons were trained to self-inject 0.32mg/kg/injection cocaine under a fixed-ration (FR) schedule, with a 3h timeout following each injection. Doses of (+/-)-N-ethyl-3, 4-methylenedioxyamphetamine HCI (MDE), (+/-)-N-hydroxy-3, 4-methylendioxyamphetamine HCI (N-OH-MDA), (+)-N-N-dimethylamphetamine HCI (NNDMA), and 4-bromo-2,5-dimethyoxy-beta-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, NNDMA 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 lever. 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.