A Point Mutation in the Cannabinoid Receptor Drives Adolescent Behavior
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Material below summarizes the article Enhanced Functional Activity of the Cannabinoid Type-1 Receptor Mediates Adolescent Behavior, on October 14, 2015, in JNeurosci and authored by Miriam Schneider, Fernando Kasanetz, Diane L. Lynch, Chris M. Friemel, Olivier Lassalle, Dow P. Hurst, Frauke Steindel, Krisztina Monory, Carola Schäfer, Isabelle Miederer, F. Markus Leweke, Mathias Schreckenberger, Beat Lutz, Patricia H. Reggio, Olivier J. Manzoni, and Rainer Spanagel.
Adolescence can be a rough and turbulent ride — not only for teenagers, but for everyone else around them. And the explanation for erratic behavior — anger, impulsivity, unnecessary risks, and inappropriate and suboptimal choices — has likely troubled parents for generations. Neuroscience first answered this mystery decades ago. Our brains, it turned out, are not fully developed at birth and undergo considerable neuronal maturation processes during adolescence until early adulthood.
We now discovered a pivotal role in adolescent brain development for an evolutionary ancient and ubiquitous neurotransmitter system in the mammalian brain, the endocannabinoid system, and its main binding site, the cannabinoid type 1 (CB1) receptor, as a crucial mediator of adolescent behavior. The cannabinoid receptors represent our body’s own natural binding sites for active components of the hemp plant, Cannabis sativa, such as D9-tetrahydrocannabinol (THC), and the receptors are involved in a plethora of physiological processes, such as pain, reward processing, emotional behavior, locomotor activity, and cognition.
In our study, we presented a rodent model with a mutation in the CB1 receptor gene, which increases the activity of the binding site. The surprising consequence: Adult mutant rats exhibit an adolescent-like phenotype with typical high risk-seeking, impulsivity, and augmented drug and non-drug reward sensitivity. Essentially, these mutants are “locked” into their adolescent state. Mutant rats, for example, are more willing to cross an area covered with a predator odor to collect a food reward, are unable to wait for a larger but delayed reward in a delay discounting task, consume higher amounts of a food reward, show enhanced social play behavior, and react with increased sensitivity to cocaine administration. Moreover, our data reveal a comparable over-activity, due to a higher availability of the CB1 receptor in wild-type adolescent rats.
Increasing our understanding of how the brain of an adolescent changes may help explain why the teenage years, for some, represent such a hazardous and highly vulnerable phase, while for others, brings peak physical strength, health, and mental capacity.
Mortality among adolescents is high, and most deaths have been reported to result from motor-vehicle crashes or other unintentional injuries, homicide, and suicide, and are often linked to the suboptimal decisions driven by the specific behavioral features of adolescence. It is also exactly during this developmental period that many neuropsychiatric disorders emerge for the first time, and the psychopathology of some of these disorders has been linked to anomalies in normal brain development.
Understanding the basis of these mental health disorders therefore requires a comprehensive knowledge of how adolescent neurodevelopment triggers behavioral reactions. Hence, our observations implicate the endocannabinoid system and the CB1 receptor as a notable research target for adolescent-onset mental health disorders. Our data demonstrate that more of these binding sites are available in the brain of adolescent rats, which may explain the higher pharmacological reactivity of adolescents towards cannabinoids, compared to adult individuals.
The more we learn, the better we may be able to understand the abilities and vulnerabilities of teenagers, and the significance of this stage for life-long mental health.
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Enhanced Functional Activity of the Cannabinoid Type-1 Receptor Mediates Adolescent Behavior. Miriam Schneider, Fernando Kasanetz, Diane L. Lynch, Chris M. Friemel, Olivier Lassalle, Dow P. Hurst, Frauke Steindel, Krisztina Monory, Carola Schäfer, Isabelle Miederer, F. Markus Leweke, Mathias Schreckenberger, Beat Lutz, Patricia H. Reggio, Olivier J. Manzoni, Rainer Spanagel. The Journal of Neuroscience Oct 2015, 35(41): 13975-13988; DOI: 10.1523/JNEUROSCI.1937-15.2015