neuropeptide-y and Amphetamine-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

Neuropeptide Y (NPY) is a 36-amino acid peptide that is widely distributed in the brain, adrenal medulla, and sympathetic nervous system. Several lines of evidence suggest a possible involvement of the NPY system in the physiological effects of several classes of abused substances including alcohol, phencyclidine, cocaine, and marijuana and in endogenous psychosis. Accordingly, it was hypothesized that the NPY system may also be involved in methamphetamine dependence or psychosis.. The single nucleotide polymorphisms rs16147 of the NPY gene (-485C>T) and rs7687423 of the NPY receptor Y1 (NPY1R) gene were analyzed in 222 patients with methamphetamine dependence and psychosis and 288 age- and gender-matched controls.. Genotypic distribution of the NPY1R gene showed a significant association with methamphetamine dependence and psychosis (P = 0.04), whereas the NPY gene had no significant association with them.. It is possible that genetic variants of the NPY1R gene affect the NPY-NPY receptor type Y1 signaling system in the brain, which may result in susceptibility to methamphetamine dependence or the development of methamphetamine psychosis, but the present findings need to be confirmed on replication.

Topics: Adult; Amphetamine-Related Disorders; Case-Control Studies; Female; Gene Frequency; Genotype; Humans; Male; Methamphetamine; Neuropeptide Y; Phenotype; Polymorphism, Single Nucleotide; Receptors, Neuropeptide Y

Club drug abuse is a growing problem in the United States. Beyond addiction and toxicity are endocrine effects which are not well characterized. Specifically, the changes in appetite following exposure to drugs of abuse are an interesting but poorly understood phenomenon. Serum hormones such as leptin, ghrelin, growth hormone (GH), and neuropeptide-Y (NP-Y) are known to affect appetite, but have not been studied extensively with drugs of abuse. In this work, we examine the effects of club drugs 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) and methamphetamine (METH) (doses of 5, 20 and 40 mg/kg) on serum concentrations of these hormones in adult male Sprague-Dawley rats 6, 12, 24 and 48 hours after drug administration. In a dose-dependent manner, MDMA was shown to cause transient significant decreases in serum leptin and GH followed by a base line recovery after 24 hours. Conversely, serum ghrelin increased and normalized after 24 hours. Interestingly, serum NP-Y showed a steady decrease in both treatment of MDMA and METH at different time points and dosages. In humans, abuse of these drugs reduces eating. As evident from these data, acute administration of METH and MDMA had significant effects on different serum hormone levels involved in appetite regulation. Future studies should be performed to see how chronic, low dose drug administration would affect hormone levels and try to answer questions about the physiological mechanisms involved in the anorexic paradigm observed in drug use.

Topics: Adrenergic Uptake Inhibitors; Amphetamine-Related Disorders; Animals; Appetite; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Ghrelin; Growth Hormone; Leptin; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Neuropeptide Y; Radioimmunoassay; Rats; Rats, Sprague-Dawley