Marijuana abuse by today’s teenagers is a major health concern because of the increased risk for emergence of cognitive and emotional dysfunctions that are traits among the RDoC-described symptoms of multiple psychiatric disorders that involve dysfunctions in the prefrontal cortex (PFC) and associated limbic brain regions. The mission of my laboratory is to establish the cellular signaling mechanisms underlying the deleterious long-term effects of marijuana on maturation of prefrontal cortical networks controlling cognitive functions which are often worsened by emotional stress such as social isolation during adolescence. This will be achieved using a multidisciplinary approach including molecular, structural, electrophysiological and behavioral measures in mouse models. These include chronic exposure of periadolescent mice to isolation stress and/or chronic administration of marijuana’s psychoactive compound, delta-9-tetrahydrocannabinol (THC) that acts mainly through cannabinoid-1 receptors (CB1Rs) in brain. This research will provide basic science information that is critical for design of improved therapeutic interventions for prevention and/or treatment of developmentally regulated frontal cortical dysfunctions. Together, the results may have far reaching implications for understanding and devising new treatment strategies for treating the many neurological and psychiatric disorders whose symptoms are worsened by adaptive changes in the brain circuitry.
The major short term goals are to complete ongoing studies of the subcellular distribution of CB1Rs identifies sites within the PFC network where chronic adolescent administration of THC can suppress the postsynaptic assembly of functional NMDA receptors. This study involves the use of electron microscopic immunolabeling and patch clamp recording in the medial (m) PFC of adult male mice that received escalating doses (2.5-10 mg/kg/ip) of THC through peri-adolescence. We are also initiating new studies of the impact of social isolation on neural circuitry involved in the mediation of anxiety-like behaviors.