Imaging corticotropin-releasing-factor and nociceptin in addiction and PTSD models

Abstract

Addiction is composed of three phases: intoxication, withdrawal, and craving. Negative reinforcement, strengthening a behaviour by removing an aversive stimulus, has been associated with the withdrawal phase. An imbalance of neurotransmitters within the brain’s stress (nociceptin, neuropeptide Y) and anti-stress (CRF, norepinephrine, etc.) system is attributed to negatively reinforced compulsive behaviours associated with relapse. Similarly, post-traumatic stress disorder is characterized by an overactive stress system. In a PTSD mouse model, rodents exhibited impaired cued-fear memory consolidation when nociceptin transmission was blocked. Furthermore, a single-nucleotide polymorphism has been identified between women diagnosed with PTSD and the severity of PTSD symptoms, suggesting a genetic basis. Therefore, it is critical to understand the functions and interactions between the brain’s stress and anti-stress neurotransmitters, specifically nociceptin. This paper will examine the hypothalamic-pituitary-adrenocortical axis, evaluate the functions of corticotropin-releasing-factor and nociceptin, discuss nociceptin’s role as an anxiolytic or anxiogenic, and discuss PET-imaging studies—all of which targeted nociceptin receptors (NOP-R). Finally, the discussion of pharmacological interventions will be proposed as preventative or therapeutic treatments for those suffering from PTSD and substance-use disorders.

Keywords:

• Nociceptin
• stress
• cortiso
• NOP-1A
• PET-imaging
• post-traumatic stress disorder
• addiction
• substance-use disorder
• HPA-axis
• radiotracers

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.