Drug addiction is a chronic, relapsing brain disease that results in major health, societal, and economic burdens. Understanding the biology of this disease is the best way to optimally design and develop effective treatments. Interactions among stress, negative mood states and drugs of abuse alter the chemistry and function of the brain such that drug addiction can develop in vulnerable individuals. Research in Dr.Chartoff’s lab focuses on the neurobiological mechanisms that connect these factors and lead to addiction, with a particular emphasis on opioid addiction.

The Chartoff lab investigates the molecular, biochemical, and cellular mechanisms underlying drug dependence and withdrawal using animal behavioral models with high relevance to the human condition. The lab includes both females and males in their studies because there is striking evidence, both clinically and preclinically, for sex differences in every facet of the addiction cycle.

The two primary lines of research in the lab are 1) understanding how the neuropeptide dynorphin mediates the link between stress, negative mood states, and addiction, and 2) understanding how excitatory glutamatergic transmission within select brain circuits is necessary for drug withdrawal-induced negative mood states, drug craving, and relapse. In the first line of research, we have shown that dynorphin is necessary for drug withdrawal-induced anhedonia, a hallmark sign of depression. Importantly, we have shown that males are significantly more sensitive than females to the anhedonic-like effects of dynorphin, suggesting that the neurobiological mechanisms underlying drug addiction are different between males and females. Our continuing efforts in this area include testing the ability of chemicals that block dynorphin function to reduce behavioral measures of addiction in our rodent models and parsing out the molecular and anatomical mechanisms for sex differences in dynorphin function. In the second line of research, we have shown that activation of AMPA glutamate receptors in the nucleus accumbens, a brain structure critical for reward function, is necessary for opioid withdrawal-induced negative affective states. Continuing efforts in this area are aimed at identifying the cellular, molecular, and neural circuit based mechanisms through which AMPA receptors are engaged to produce negative affective states and how this contributes to addictive behavior.

Together, these studies may lead to an increased understanding of the mechanisms underlying addiction. They also have broad implications for understanding basic brain mechanisms that control mood and motivated behavior.