Modeling human methamphetamine exposure in nonhuman primates: chronic dosing in the rhesus macaque leads to behavioral and physiological abnormalities.

Abstract

Acute high dose methamphetamine (METH) dosing regimens are frequently used in animal studies, however, these regimens can lead to considerable toxicity and even death in experimental animals. Acute high dosing regimens are quite distinct from the chronic usage patterns found in many human METH abusers. Furthermore, such doses, especially in nonhuman primates, can result in unexpected death, which is unacceptable, especially when such deaths fail to accurately model effects of human usage. As a model of chronic human METH abuse we have developed a nonlethal chronic METH administration procedure for the rhesus macaque that utilizes an escalating dose protocol. This protocol slowly increases the METH dosage from 0.1 to 0.7 mg/kg b.i.d. over a period of 4 weeks, followed by a period of chronic METH administration at 0.75 mg/kg b.i.d. (= total daily METH administration of 1.5 mg/kg). In parallel to human usage patterns, METH injections were given 20-23 times a month. This regimen produced a number of behavioral and physiological effects including decreased food intake and a significant increase in urinary cortisol excretion.