ongoing research projects

Adolescence is a critical time during development, and exposure to adversities during this period disrupts typical development resulting in a myriad of debilitating neuropsychiatric disorders, including addiction. The nucleus accumbens (NAc) plays a critical role in anxiety, stress, motivation, and reinforcement-learning related processing. Here we use an adolescent social isolation model to examine neural perturbations that lead to maladaptive behaviors. Our research has discovered that kappa opioid receptors (KORs) in the NAc possess great sensitivity to both dynorphin and various agonists after a history of prolonged adolescent stress. KOR activation is known to decrease dopamine tone in the NAc leading to an anhedonic-like state, which potentially drives maladaptive behaviors. Here we seek to establish a potential causal relationship between KORs in the NAc and their regulatory actions on dopamine release, anxiety-like behaviors, and heightened vulnerability to develop alcohol and substance use disorders in rats exposed to chronic adolescent stress.

Chronic intermittent ethanol vapor (CIE) exposure is a well-validated rodent model of ethanol dependence. CIE exposure results in excessive ethanol intake, disruption of dopamine signaling, and an upregulation in KOR function. We have observed similar neural changes in the NAc following adolescent social isolation, which leads to behavioral hallmarks seen in PTSD. We are interested in examining behavioral responsivity to ethanol exposure following adolescent social isolation. In addition, the goal of this project is to examine whether the neural changes observed are additive or synergistic when combined with exposure to stress and alcohol exposure. Ongoing experiments are examining whether KORs, in combination with other proteins, play a causal role in augmenting addiction vulnerability and PTSD-like behavioral symptoms following prolonged adolescent stress exposure and CIE.

A person’s first exposure to opioids often begins in the clinic—likely for acute pain. Before CDC regulations on prescribing opioids changed, many patients were able to easily receive a prescription for opioids. Many times their pain had even subsided, and the dangers of opioid misuse prevailed until development of an opioid use disorder. Rising costs of opioids, and difficulty of receiving a long-term prescription for opioid, led many people to obtaining heroin on the street. The goal of this project is to identify neural underpinnings and the individual differences that drive the development of opioid misuse to opioid use disorder. These studies combine circuit mapping techniques with a wide range of behavioral and neurochemical techniques to determine whether exposure to stress augments motivation to consume opioids.

Stress, especially during adolescence, alters typical development of the catecholamine systems, as well as development of other proteins that interact with the catecholamine system. As mentioned in other projects, our research has shown that the KOR function is upregulated. KORs interact with several other adjacent receptor proteins at the dopamine terminal that also interact with cocaine. Behaviorally, we have shown that adolescent social isolation stress increases the motivation to self-administer cocaine. The goal of this project is to examine the interaction of two functionally connected proteins (for example, KORs and dopamine receptors), and then identify the prolonged adolescent stress exposure-induced alteration in this functional relationship, which could potentially alter cocaine seeking behaviors. This information can then be used to restore the receptors' function via pharmacological treatments.