Circuit and neuropeptide mechanisms of the paraventricular thalamus across stages of alcohol and drug use.

The paraventricular nucleus of the thalamus (PVT) is a midline thalamic brain region that has emerged as a critical circuit node in the regulation of behaviors across domains of affect and motivation, stress responses, and alcohol- and drug-related behaviors. The influence of the PVT in this diverse array of behaviors is a function of its ability to integrate and convey information about salience and valence through its connections with cortical, hypothalamic, hindbrain, and limbic brain regions. While understudied to date, recent studies suggest that several PVT efferents play critical and complex roles in drug and alcohol-related phenotypes. The PVT is also the site of signaling for many neuropeptides released from the synaptic terminals of distal inputs and local neuropeptidergic neurons within. While there is some evidence that neuropeptides including orexin, neurotensin, substance P, and cocaine and amphetamine-related transcript (CART) signal in the PVT to regulate alcohol/drug intake and reinstatement, there remains an overall lack of understanding of the roles of neuropeptides in the PVT in addiction-related behaviors, especially in a circuit-specific context. In this review, we present the current status of preclinical research regarding PVT circuits and neuropeptide modulation of the PVT in three aspects of the addiction cycle: reward/acquisition, withdrawal, and relapse, with a focus on alcohol, opioids (particularly morphine), and psychostimulants (particularly cocaine). Given the PVT's unique position within the broader neural landscape, we further discuss the potential ways in which neuropeptides may regulate these behaviors through their actions upon PVT circuits. This article is part of the special Issue on 'Neurocircuitry Modulating Drug and Alcohol Abuse'.