The usefulness of non-human primates in central nervous system safety pharmacology

Abstract

Introduction: The present paper will suggest, on the basis of experimental evidence, that several non-human primate (NHP) procedures can be uniquely useful and relevant for central nervous system (CNS) safety pharmacology purposes.

Methods and results: Classical antipsychotics (e.g. haloperidol) but not atypical antipsychotics (e.g. clozapine), in contrast to rodents, induce behavioral signs in NHP which are clearly homologous to those observed in humans and thus have high translational value. Operant techniques (delayed matching/non-matching-to-sample) and non-operant techniques (object retrieval) can be used in NHP to assess the facilitating and impairing effects of drugs on cognition. Brain structures sub-serving these functions are closer to humans in NHP than in rodents suggesting that drug data from NHP translate better to humans. Biting into a rubber tube can be induced in squirrel monkeys by exposure to non-reinforcement (frustration). This model is close to human notions of frustration/aggression, and is ethically more acceptable than methods using shock or animal fighting. It could therefore serve as a model of drug-induced irritability with potentially high translational value.

Conclusion: There are cogent scientific reasons for selecting NHP in CNS and other safety pharmacology areas.

Keywords: Biting; Cognition; Delayed matching/non-matching-to-sample; Dystonia; Executive function; Extrapyramidal symptoms (EPS); Frustration-aggression; Methods; Non-human primates (NHP); Object retrieval.