RESEARCH

The main goal of our research is to identify the neural circuits controlling motivated behaviors, primarily those controlling drug seeking. We are especially interested in understanding how these circuits change as the animal takes more and more drug over time, and how these changes alter the ability of drug-associated cues to trigger relapse. We are also interested in circuits controlling the inhibition of learned behaviors and the active suppression of motivational impulses. Using preclinical self-administration models of addiction (substance use disorder), we have discovered the infralimbic prefrontal cortex is a key component of the neural circuitry responsible for inhibiting drug seeking. Much of our work focuses on neuroanatomical inputs and outputs to/from this brain region. We use optogenetic and chemogenetic viral strategies to manipulate neuronal activity within defined neural pathways and cell types and fiber photometry to record neuronal population activity with calcium sensors (GCaMP, RCaMP) in vivo during behavioral tasks. In addition to these techniques, the lab also routinely uses immunohistochemistry and confocal microscopy to visualize and image the neurons we manipulate, as well as perform neuroanatomical tracing and Fos expression analyses (Fos = a biochemical marker for neuronal activation).

The prefrontal cortex may also be a key brain region whereby psychedelic drugs elicit their therapeutic effects on emotional behavior and substance use disorders. While many psychedelics are controlled substances, they do not usually come with addiction liability. Psychedelics are part of a broader group of substances known as psychoplastogens, for their "mind-melding" properties, referring to their ability to induce structural plasticity. Psychoplastogens increase dendritic complexity and spine density both in vitro and in vivo, and the 5-HT2A receptor has been implicated in these effects. The 5-HT2A receptor has also been implicated in the hallucinatory effects of many psychedelics. However, some research suggests that the hallucinatory and therapeutic effects of psychoplastogens are dissociable. We are interested in screening 5-HT2A agonists as potential therapeutics for treating substance use disorders in our self-administration models and using this information to guide the development of better 5-HT2A ligands for clinical translation.

We are also engaged in translational applications of our work through the Center for Clinical and Translational Science at UAB.