Willingness to continue seeking and taking alcohol despite negative consequences suggests impairment of neural circuits encoding reward and aversion and/or driving adaptive responding in the face of changing outcomes. The rostromedial tegmental nucleus (RMTg) exerts inhibitory control over mesolimbic dopamine neurons and is critically involved in aversive signaling. The prelimbic (PL) subregion of the prefrontal cortex shares several critical functional similarities with the RMTg including facilitating aversion learning and responding to aversive stimuli. Despite these similarities, the projection from the PL to the RMTg has been largely ignored and remains an open area of investigation.
The aims of the parent grant are focused on understanding the role that PL inputs to the RMTg play in alcohol abuse and dependence. However, the RMTg also receives input from the neighboring infralimbic (IL) prefrontal cortex ? an area which is thought to have opposing actions to those of the PL cortex. While the parent grant hypothesizes that uncontrolled and compulsive drinking is driven via a dependence-induced reduction in PL-RMTg activity, it is also possible that IL-RMTg activity is enhanced following dependence, thereby facilitating continued alcohol consumption. The experiments proposed under this administrative supplement will investigate this possibility by characterizing the function of IL input to the RMTg in alcohol dependent and non-dependent rats. The findings we uncover will allow us to functionally discriminate between PL and IL inputs to the RMTg and better understand how dependence-induced alterations in these neural circuits contribute to altered drinking behavior. Award of this administrative supplement will further allow the candidate, a promising, black, African American woman, the opportunity to gain in-depth experience in alcohol research and receive mentorship that will allow her to develop further at the graduate level so that she may continue pursuing a career in alcohol research.
Continued alcohol consumption despite negative consequences is a hallmark of addiction, yet the neurobiological mechanisms underlying this phenomenon are not well-understood. Recent work has identified a midbrain nucleus known as the rostromedial tegmental nucleus (RMTg) in the processing of aversive stimuli. The project proposed in the current application will examine the role that RMTg-projecting infralimbic neurons play in mediating uncontrolled and compulsive alcohol drinking.
