Long-term methamphetamine induced changes in brain catecholamines in tolerant rhesus monkeys.

(Received September 1, 1975) : d-Amphetamine, methamphetamine and other phenethylamines cause decreases in food intake, stereotypic behavior, disruption of behavior that is under stimulus control, as well as general sympathomimetic effects such as hyperthermia, increased blood pressure and piloerection. The doses required to produce different effects vary. In addition, most psychomotor stimulants are subject to abuse in man and will be self-administered by animals [ 1]. Repeated administration of the amphetamines leads to the development of tolerance to many of its effects on behavior although the degree of tolerance depends to a large extent on the frequency of administration, the dose, the route of administration and the behavior in question. Several p investigators have presented evidence that amphetamines exert their effects upon behavior by increasing the concentration of catecholamines at the synaptic cleft by blocking re-uptake and/or promoting release. The overall purpose of this investigation was to determine the effect of long-term repeated intravenous administration of methamphetamine in increasing doses to rhesus monkeys. This study was part of a larger research program designed to determine if long-term administration of methampheta-mine results in irreversible effects in the rhesus monkey. To this end, measures were made on behavior, neuropathology and brain catecholamines. In this paper we shall report both short and long-term changes in brain cate-cholamines that were caused by prolonged administration of methampheta-mine. It was found that methamphetamine induced changes in regional brain catecholamines, some of which persisted even after the drug was discontinued. Rhesus monkeys were injected intravenously 8 times daily. The dose of methamphetamine was increased until a final dose was reached which could through observing diminished food intake and weight loss. Doses were incremented only when signs of behavioral tolerance appeared. Two studies were carried out: in the first, monkeys were treated for 3-6 months {final dose 3.0-6.5 mg/kg/inj) eight times per day. Monkeys were either killed 24 hours or 3-6 months after the last injection. In the