Transgenic and Knockout Models of Psychiatric Disorders

Abstract

Humans have long distinguished themselves from infrahuman organisms. Modern notions of humans and infrahuman animals, however, date from the mid-19th century and are essentially derived from Darwin’s The Origin of Species. Although Darwin differentiated between acquired habits in humans and inherited instincts in animals, his theory of evolution embraced the notion of continuity of species. Late-19th and early-20th century animal psychologists debated this issue; particularly, whether animals had minds, and, if so, whether they were capable of the same thought and emotion evinced in humans. To avoid the problems created by mentalism and consciousness in animal behavior, many leading psychologists of the time adopted the mechanistic assumption, as extant among the British associationists. Others, however, subscribed to the belief that animals were capable of problem solving that went beyond the simple conditioning paradigm incorporating the principle of reinforcement. As a formal approach, operant conditioning was instrumental in providing many important results and was an effective epistemological framework in which to view animal and human behavior. For many psychologists, however, behaviorism seemed limited to what could be inferred from bar pressing and key pecking. As enthusiasm for behaviorism ebbed, cognitive psychology began to assert its influence, restoring the concepts of mentalism to and consciousness in animals, and directing its research efforts to intelligence and problem solving. At approximately the same time, other related areas in science—neurobiology, genetics—converged onto issues related to learning and memory, the result of which was the emergence of cognitive neuroscience. The revolution in genetics brought about by the discovery of the structure of DNA, along with the discovery of genetic abnormalities associated with learning disabilities, accelerated research into genetics factors that produced mental retardation and psychopathology. Cognitive psychology and cognitive neuroscience provided the epistemological justification for using animal models to explore various forms of human cognitive impairment. Studies in neuroscience using recently developed behavioral procedures have identified brain structures associated with certain features of learning and emotion. Successful development of knockout and transgenic technologies, followed by the creation of mouse models of genetic disorders, were used to identify many of the neurobiological and neurophysiological functions associated with neurobehavioral disorders. However, mice are not humans and the question regarding whether studies of animal behavior are relevant to human thought, problem solving, intelligence, and emotions has not been resolved.