Kourrich Lab Members
Front (L-R): Saïd Kourrich, Ph.D; Deena Sajitharan; Francisco Garcia-Oscos; Mohammad Housini; Back: Amir Segev, Ph.D.

Our Research

Over the last few decades, there has been a drastic shift in the societal perception of drug addiction, from a personality flaw characterized by a lack of self-control to the classification of addiction as a chronic neuropsychiatric disorder. This change has been facilitated by surmounting evidence derived from neurobiological research focused on asking questions about why and how individuals become addicted to drugs. Studies seeking to understand why people become addicted to drugs of abuse attempt to pinpoint what factors make an individual predisposed to develop addictive disorders, i.e., biological differences that exist before an individual is exposed to a drug of abuse. Our research focuses on how individuals become addicted; and more specifically, how neurobiological modifications triggered by drug experiences alter neuronal activity, and thereby lead to maladaptive behaviors that characterize drug addiction.

Essentially, two excitability factors contribute to the shaping of global neuronal activity, synaptic and intrinsic. While the first is mainly controlled by excitatory synaptic glutamatergic transmission, the second is controlled by intrinsic membrane properties, i.e., non-synaptic factors. Conceptually, these non-synaptic factors include any elements located on the soma, dendrites, or axon, which are “remote” from the synapse, but either passively or actively modulate membrane excitability. Although our research investigates how both synaptic and intrinsic factors are modulated by drugs, we put a particular emphasis on drug-induced changes in active intrinsic membrane properties, i.e., the factors that directly contribute to the generation of action potentials and the characteristics of repetitive firing—processes that are mainly controlled by interplay between Na+, K+, and Ca2+ channels.

Neuron Diagram

Briefly, regarding the nucleus accumbens (NAc), a brain region that is involved in reward and motivation, it is now well established that cocaine experience affects both excitability factors. Questions that are still unresolved or points that are still discussed are how drug-induced changes in synaptic and intrinsic factors interact with one another to shape maladaptive global neuronal excitability, the cellular mechanisms through which cocaine affect these factors, and their causal relationships with addiction-relevant behaviors. Using a multidisciplinary approach, combining behavior, pharmacology, biochemistry, and electrophysiology, our research will aim to provide insights into these questions.