neuropeptide-y and Cocaine-Related-Disorders

Neuropeptide Y (NPY) is a neuromodulator that is widely expressed throughout the central nervous system (CNS) and which is cosecreted with classic neurotransmitters including GABA and glutamate. There is a long history of research implicating a role for NPY in modulating neurobiological responses to alcohol (ethanol) as well as other drugs of abuse. Both ethanol exposure and withdrawal from chronic ethanol have been shown to produce changes in NPY and NPY receptor protein levels and mRNA expression in the CNS. Importantly, manipulations of NPY Y1 and Y2 receptor signaling have been shown to alter ethanol consumption and self-administration in a brain region-specific manner, with Y1 receptor activation and Y2 receptor blockade in regions of the extended amygdala promoting robust reductions of ethanol intake. Similar observations have been made in studies examining neurobiological responses to nicotine, psychostimulants, and opioids. When taken together with observations of potential genetic linkage between the NPY system and the human alcohol abuse disorders, NPY represents a promising target for treating problematic alcohol and drug use, and in protecting individuals from relapse during abstinence.

Topics: Alcohol Drinking; Alcohol-Related Disorders; Amphetamine-Related Disorders; Animals; Cocaine-Related Disorders; Humans; Neuropeptide Y; Opioid-Related Disorders; Receptors, Neuropeptide Y; Tobacco Use Disorder

Introduction The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has a key role in drug addiction susceptibility. In addition to the well-known relationship between cortisol and the HPA axis, other molecules are involved with stress response and could modify the HPA activation, such as the neuropeptide Y (NPY), which has anxiolytic proprieties. There are few studies evaluating the effect of NPY levels on addiction, especially in crack cocaine dependence. Objective To evaluate NPY in crack users during early withdrawal to determine its relationship with drug use and cortisol levels. Methods We analyzed 25 male inpatient crack users. Serum NPY levels were measured at admission and discharge (mean of 24 days). Morning salivary cortisol was measured at admission. Results Serum NPY levels at admission and discharge were very similar. Lower NPY levels at discharge were associated with higher lifetime crack use. Also, a negative correlation was found between morning cortisol and delta NPY (NPY discharge - NPY admission). Conclusion These preliminary findings indicate that crack use influences the modulation of NPY levels and modifies stress response. The NPY pathway may play an important role in the pathophysiology of crack addiction, and the anxiolytic effect of NPY may be impaired in crack users. Future studies should consider NPY as a measurable indicator of the biological state in addiction.

Topics: Adult; Cocaine-Related Disorders; Crack Cocaine; Humans; Hydrocortisone; Inpatients; Male; Middle Aged; Neuropeptide Y; Stress, Psychological; Substance Withdrawal Syndrome

There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction. Whether this is due to an observed compensatory increase in striatal dopamine transporter binding or an anxiogenic phenotype of the transgenic mice remains to be determined.

Topics: Animals; Cocaine; Cocaine-Related Disorders; Mice; Mice, Knockout; Neuropeptide Y