The role of HCRTR and NPSR genes in the pathogenesis of methamphetamine addiction

Addiction is a chronic disease in which neurodevelopmental, genetic and sociocultural factors play a role. It is characterized by compulsive seeking and taking certain substances and chemicals, despite all its serious physical and psychological negative effects on individuals. Methamphetamine, one of the most frequently abused illicit psychostimulants, is a potent and addictive stimulant that affects the central nervous system. Methamphetamine triggers the release of dopamine, serotonin, noradrenaline and adrenaline from nerve terminals in the central and peripheral nervous system. Also, it has been found to modulate at least three different molecular mechanisms, such as oxidative stress, neuroinflammation, and neurotoxicity. Many neuronal circuits in the brain have been associated with the development of addiction, and recent studies have suggested that the orexinergic neurons in the hypothalamus and the neuropeptide S system, which is closely related to these neurons, may play a role in the development of addiction. In our study, the frequencies of HCRTR1 rs2271933 and rs41263963, HCRTR2 rs2653349, NPSR rs324981gen polymorphisms and Orexin A serum levels were determined in patients with methamphetamine use disorder (MUD) and healthy controls. In this study, it was aimed to investigate the roles of these parameters in the pathogenesis of MUD. One hundred seventy three patients diagnosed with MUD and 102 healthy controls were included in the study. Between the groups, serum Orexin A levels were found to be significantly lower in the MUD group compared to the control group. In addition, it was determined that MUD patients had higher orexin A levels in the post-detoxification craving periods compared to the pre-cleansing periods. There was no statistically significant difference between the patient and control groups in terms of genotype and allele frequency distribution of HCRTR1 rs2271933 and rs41263963, HCRTR2 rs2653349, NPSR rs324981gen polymorphisms. In conclusion, it is thought that Orexin A level is effective in the pathogenesis of MUD and its episodes, and it is expected that the role of hypocretin and neuropeptide S receptor polymorphisms and orexin A level in the pathogenesis of MUD will be understood more clearly with future studies on larger populations.