Review: Non-human primate models of inheritance vulnerability to alcohol use disorders (Barr & Goldman)
by Kaitlyn May
Non-human primates provide a useful model for studying the influence of genetic factors on alcohol consumption. The complex social structures, behaviors, and genetics of non-human primates parallel humans, and thus are fruitful models for research. Animal models are particularly useful for studying the interaction of genetics with social environments, and because of this they are critical to our understanding of neuroadaptive processes.
The article provides a review of the utility of using non-human primates to study alcohol use in humans. Laboratory animals offer an easy way to model consumption, withdrawal, tolerance, dependence, sedative and reward effects, and neurobiological effects in a way that mirrors those in humans. Most notably, non-human primate models provide the opportunity to study genetic influences on alcohol consumption and alcohol-related phenotypes in a highly social animal model that is genetically close to humans.
Non-human primate models add to our understanding of inheritance vulnerability to alcohol use disorders in humans along multiple indices. First, non-human primates can be followed from birth or pre-birth, and alcohol exposure can be tightly controlled throughout development. Following humans in longitudinal research is difficult, and humans who are already alcohol-exposed, even prenatally, have neurochemical, physiological, and behavioral differences. Moreover, this ability to tightly control the experimental environments of laboratory animals enables the experimenter to reduce confounds and increase the power and sensitivity of genetic and neurobiological analyses. Because of this, animal models are ideal for studying gene by environment (GxE) interactions.
Rhesus macaques demonstrate individual differences in alcohol response and temperament, and the relation of the these differences to genetic variants. Because these genetic variants are also present in humans these models are important to discussing GxE interactions. For example, rhesus macaques can be used to develop experimental models of early adversity, such as loss of a parent, as models of early adversity and their relationship to voluntary alcohol consumption.
Moreover, non-human primates are useful to modeling the behavioral and social effects of alcohol use disorders. Non-human primates are social animals that live in highly structured hierarchies with social norms and relationships. Non-human primates that continue to consume alcohol even though it disrupts social interactions provide a model of the disruption of interpersonal relationships that is characteristic of alcohol use disorders. Likewise, individual differences in temperament, and its relation to alcohol use disorders, can be explored via non-human primate models.
Still, there are limitations to using non-human primate models to understand alcohol use in humans. Animal models are unable to communicate subjective states, and this limits assessment of subjective differences in alcohol response. In addition, some animals have nervous systems that are much simpler than the human nervous system. On top of this, there are ethical issues when using non-human primates. Moreover, rodent lines offer controlled genetic diversity via selective breeding and transgenic/knockout lines—something that non-human primates cannot yet offer. Inbred primates are unavailable, and transgenic primates have not been successful. Further, rodent models are easier to breed, have large litters, are fairly inexpensive, and have accelerated developmental trajectories.
The authors conclude their review with a discussion of candidate genes influencing alcohol-related disorders. These polymorphisms, rh5-HTTLPR, MAOA-LPR, and OPRM1 C77G have been shown to influence alcohol consumption in rhesus macaques. Moreover, studies seeking to identify polymorphisms have pointed to variants in the coding and regulatory regions of multiple genes in rhesus macaques. These studies point to the need for further studies, using non-human primates, exploring genes influencing behavior or alcohol consumption and response. The authors then provide a brief discussion of genetic and environmental interactions. Non-human primates are particularly useful for the study of GxE interactions because their environments can be tightly controlled.
1. Do you think that the benefits outweigh the limitations when using non-human primates in research?
2. How can non-human primates be used in a neuroanthropological study? How would you design a research study using these methods?