Utility of Nonhuman Primates in Substance Use Disorders Research

Abstract

Substance use disorders (i.e., drug addiction) constitute a global and insidious public health issue. Preclinical biomedical research has been invaluable in elucidating the environmental, biological, and pharmacological determinants of drug abuse and in the process of developing innovative pharmacological and behavioral treatment strategies. For more than 70 years, nonhuman primates have been utilized as research subjects in biomedical research related to drug addiction. There are already several excellent published reviews highlighting species differences in both pharmacodynamics and pharmacokinetics between rodents and nonhuman primates in preclinical substance abuse research. Therefore, the aim of this review is to highlight three advantages of nonhuman primates as preclinical substance abuse research subjects. First, nonhuman primates offer technical advantages in experimental design compared to other laboratory animals that afford unique opportunities to promote preclinical-to-clinical translational research. Second, these technical advantages, coupled with the relatively long lifespan of nonhuman primates, allows for pairing longitudinal drug self-administration studies and noninvasive imaging technologies to elucidate the biological consequences of chronic drug exposure. Lastly, nonhuman primates offer advantages in the patterns of intravenous drug self-administration that have potential theoretical implications for both the neurobiological mechanisms of substance use disorder etiology and in the drug development process of pharmacotherapies for substance use disorders. We conclude with potential future research directions in which nonhuman primates would provide unique and valuable insights into the abuse of and addiction to novel psychoactive substances.

Impaired cognitive behavioral flexibility following methamphetamine or high caloric diet consumption: a common 5-HT2C mechanism?

“…Overall, Perez Diaz et al [4] provide compelling preclinical evidence that 5-HT 2C activation decreases perseverative behavior regardless of experimental drug or diet history. The use of nonhuman primates as research subjects in the Perez Diaz et al [4] enhances the potential translatability of these findings to positive clinical outcomes [8]. The current opioid and obesity public health crises has reinvigorated preclinical and clinical research efforts to develop safer and more effective treatment.…”

Establishing Preclinical Withdrawal Syndrome Symptomatology Following Heroin Self-Administration in Male and Female Rats

“…Thus far, efforts to reliably predict opioid withdrawal severity in humans have 59 been largely unsuccessful, with studies attributing differences in withdrawal presentation to 60 several different demographic and drug use characteristics. 61 A recent review outlined the numerous species that are used for preclinical evaluation of 62 substance use disorders (Smith, 2020), including invertebrate, rodent (de Guglielmo et al, 2017), 63 and nonhuman primate models (Banks et al, 2017;Katz, 1986; Schwienteck, Negus, & Banks, 64 2019). These models provide a method by which correlates and underlying mechanisms of 65 different opioid withdrawal symptoms can be precisely evaluated, and have been used in the past 66 to directly support clinical evaluation of various withdrawal pharmacotherapies.…”

An assay of drug‐induced emesis in the squirrel monkey (Saimiri sciureus)

“…The aim of the present studies was to fill this knowledge gap by examining the emetic response in the squirrel monkey ( Saimiri sciureus ). Well‐established behavioral and pharmacological methodologies in this species have provided a rigorous approach to the study of psychoactive drugs for over 60 years, including investigations of abuse liability, subjective effects, cognitive impairment, and structural, functional, and neurochemical consequences of acute and chronic drug exposure . In addition, this species is small compared to other common laboratory non‐human primates, such as macaques, resulting in relatively simplified husbandry and handling.…”

“…Well-established behavioral and pharmacological methodologies in this species have provided a rigorous approach to the study of psychoactive drugs for over 60 years, including investigations of abuse liability, subjective effects, cognitive impairment, and structural, functional, and neurochemical consequences of acute and chronic drug exposure. [38][39][40][41][42][43][44][45][46] In addition, this species is small compared to other common laboratory non-human primates, such as macaques, resulting in relatively simplified husbandry and handling. They also carry a relatively low risk of transmitting zoonotic infections to researchers.…”