The major driving force behind cocaine relapse is drug craving. The most widely accepted preclinical model to study this craving involves training animals to self-administer drugs, extinguishing this responding by removing the drug reinforcer, and subsequently eliciting reinstatement of responding.  Stressful experiences and cues previously paired with drug use elicit craving in human addicts and reinstate extinguished cocaine seeking behavior in this reinstatement model. Our laboratory utilizes a variety of techniques including behavioral pharmacology, mouse genetics, molecular biology, and electrophysiology to study how the brain responds differently to stress and cues after cocaine self-administration experience.

Cocaine Experience Leads to Alterations in Glutamatergic Synapses

Following chronic cocaine abuse, neuroadaptations occur in the glutamatergic neurotransmitter system. One of these types of adapatations involves alterations in the composition of one type of glutamate receptor, the AMPA receptor. Activity dependent insertion and removal of AMPA receptors represents a critical form of synaptic plasticity. This activity dependent AMPA receptor trafficking is mediated by many second messenger systems and scaffolding proteins. Current work, funded by the National Institute on Drug Abuse, utilizes mutant mouse models and electrophysiology to study the role of the scaffolding proteins GRIP and PICK in the ability of cues and stress to elicit relapse.

Disrupting Glutamate Trafficking in the Prefrontal Cortex leads to Cognitive Deficits

Cocaine addicts exhibit deficits in executive function and the extent of these deficits can be predictive of treatment outcomes. Addicts have trouble changing behavioral patterns in the face of long-term negative consequences. Alterations in glutamatergic signaling within the PFC can lead to impaired cognitive performance like that seen in cocaine addicts. However, the mechanisms by which glutamatergic alterations in the PFC affect cognitive function and addictive phenotypes are unknown. Current work is examining how disrupting AMPAR trafficking within the mPFC, by deleting glutamate receptor interacting protein (GRIP), alters both cocaine seeking and cognitive function.

Adolescent Stress Leads to Increased Vulnerability to Addiction

Stressful experiences during adolescence can lead to increased drug use and addiction. This may be due, in part, to the effect of these drugs in the developing adolescent brain or be a direct result of the ability of stress to permanently alter neurophysiology during adolescence. Current work in the lab is aimed at examining how adolescent stress alters the brain’s response to cocaine both during adolescence and adulthood.