Schizophrenia

CB1 cannabinoid receptor activation during adolescence impairs maturation of prefrontal GABAergic circuits
2012 Seed Grant
Kuei Tseng, M.D., Ph.D.
Department of Cellular and Molecular Pharmacology
Rosalind Franklin University

The late-adolescent onset of psychiatric and addiction-related syndromes is strongly linked to the sensitive period of prefrontal cortex (frontal lobe) maturation during adolescence. However, the neurodevelopmental processes that determine this vulnerability are currently unknown. Among the different neurotransmitter candidates thought to confer predisposition to the adolescent liability, the brain CB1 cannabinoid receptor, which mediates the psychoactive effects of marihuana (cannabis), is of particular interest due to recent studies showing that marihuana abuse during adolescence significantly increase the risk of developing schizophrenia later in life. Interestingly, CB1 receptors are highly expressed in the prefrontal cortex. What is missing is the mechanistic link between the effects of repeated cannabinoid exposure during adolescence and the development of prefrontal cortex dysfunction. Thus, the goal of Dr. Tseng’s study is to establish such a mechanistic link by determining whether repeated activation of the CB1 receptor limited to the adolescent period is sufficient to impair the normal maturation of the prefrontal cortex network, and its association with prefrontal-related behavioral deficits in adulthood.