Preclinical Models of THC and Nicotine Exposure During Adolescent Brain Development: Modeling Neuropsychiatric Phenotypes Related to Dopaminergic Transmission

Abstract

Adolescence is a gradual transition period between childhood and adulthood, characterized by greater sensitivity to rewarding stimuli. Consistently, demographic studies have shown that teenagers show a high prevalence of rewarding drugs use, mainly nicotine-containing products and cannabis. Clinical researches have associated the adolescence consume of nicotine and cannabis with a higher vulnerability to develop neuropsychiatric diseases in adulthood such as depression, schizophrenia, and drug addiction. Despite these evidence, it is difficult to conclusively prove causal relationships with longitudinal and retrospective clinical research in humans. Accordingly, preclinical animal models are indispensable tools to determine the causal relationship between early neurodevelopmental drug exposure and psychiatric disease risk. Preclinical rodent models have been widely used to research the neurobiological mechanisms underlying the vulnerability of the adolescent brain because the similarities in behavioral patterns and brain maturation processes with human adolescents. Particularly, both human teenager and adolescent rodents show similar patterns of DA maturation, and dysregulations in these neuronal circuits may induce phenotypes associated with psychiatric diseases. This chapter will describe the THC and nicotine adolescent exposure methods in rats that induce a long-term dysregulation of the dopaminergic system. Furthermore, this chapter will detail the experimental protocol used in our laboratory to test the electrical activity of dopaminergic neurons. In addition, these methodologies include preclinical testing protocols for several neuropsychiatric behavioral phenotypes related to social cognition and motivation, memory processing, and anhedonia-like behaviors.