Monkeys tolerance

The original observation of long-term depletions of DA in the rhesus monkey was made during a study of the development of tolerance to the effects of daily injections of METH (Fischman and Schuster 1977). In this study, it was found that behavioral tolerance to METH on a differential-reinforcement-of-low-rate (DRL) task persisted long after the repeated METH regimen. In a similar study conducted later, monkeys treated with repeated METH showed reduced sensitivity to apomorphine and increased... 

Seiden, L.S. Fischman, M.W. and Schuster, C.R. Long-term methamphetamine induced changes in brain catecholamine in tolerant rhesus monkeys. Drug Alcohol Depend 1 215-219, 1975-76. 

Fischman, M.W., Schuster, C.R. Tolerance development to chronic methamphetamine intoxication in the rhesus monkey. Pharmacol. Biochem. Behav. 2 503, 1974. 

In vitro TGN1412 caused a profound, polyclonal T-cell proliferation of human peripheral blood mononuclear cells, including those from patients with BCLL. It also induced a profound activation and proliferation of T-cell subsets including CD4+ and CD8+ T cells, naive and memory T cells, and regulatory T cells. TGN1412 was shown to induce a transient, well tolerated expansion of T cells in nonhuman primates treated with TGN1412 and efficacy was demonstrated in a rhesus monkey collagen-induced arthritis model. 

Keep in mind that the objective of such studies is to gain information about lethality and gross tolerance. For nonrodents (especially monkeys), if none of the animals dies or demonstrates obvious signs of toxicity, little would be gained by euthanizing and necropsying such animals. They can be saved and used again,... 

Eckstein, P., Jackson, M., Millman, N. and Sobero, A. (1969). Comparison of vaginal tolerance test of spermical preparations in rabbits and monkeys. J. Reprod. Fertil. 20, 85-93. 

In both mice and rats exposed 6 hours/day 5 days/week for 12 weeks, the no-effect dose was below 150 ppm and the maximum tolerated dose was below 600 ppm. At doses of up to 12 00 ppm there were few signs of overt toxicity, and at necropsy the only treatment related lesions occurred in the liver. Subchronic studies in monkeys showed no exposure-related adverse health effects or reproductive effects after exposure 6 hour/day, 5 days/week for 13 weeks to concentrations of up to 500ppm."... 

A single 7-hour exposure of rats to 500 ppm resulted in mild narcosis with rapid recovery. Repeated daily inhalation exposures to 3 00-400 ppm for over 100 days produced minor histopathologic liver changes in rabbits, monkeys, and guinea pigs rats initially experienced slight narcosis but developed tolerance to this effect after a few weeks. Daily exposure of rats and rabbits to 200 ppm for 13 weeks caused no effects. Topical administration of lOmg/kg five times/week for 13 weeks to... 

In monkeys and dogs, the LCso was 2 6 ppm for 1 hour signs of toxicity were lacrimation, dyspnea, muscular weakness, and vomiting at autopsy, massive pulmonary edema and hemorrhage were observed. In mice, exposure to a low concentration (1 ppm for 60 minutes) produced tolerance to subsequent exposures 8 days later at levels that would otherwise have been fatal (4.25ppm for 60 minutes). 

Early studies (1957) by Parke, Davis In monkeys showed no evidence of tolerance or persistent toxic effects in monkeys after repeated parenteral administration at 1.25 or 5 mg/kg once a day, 5 d/wk, for 43 doses. 

More recent studies, 9 12 at dosages that produce behavioral changes, have shown that chronic intramuscular or Intraperltoneal administration of SNA results in development of tolerance to several test situations In several animal species. Tolerance to roughly 2-4 times as much SNA as initially given was evident in the behavioral effects of SNA In these species. Tolerance to SNA was also observed In intramuscular SNA self-administration studies In the monkey. In the development of tolerance, such pharmacologic factors as dose per injection, Injection frequency, and duration of chronic exposure were considered to play a more Important role than behavioral factors (e.g., reinforcement loss).9... 

Hallucinogenic drugs like LSD are not reinforcing In animals, In that they will not self-admlnister these drugs. SNA, however, Is self-administered In large quantities by monkeys equipped with intravenous catheters when access is unlimited. Tolerance of the acute... 

Studies with dogs and monkeys have shown that tolerance to the toxic effects of DMHP develops.20,35,36,40,44... 

---