Estudo do papel da oxitocina sobre efeitos comportamentais associados à recompensa gerada pela nicotina em camundongos adultos e adolescentes

Abstract

Smoking is quite common in high-, middle- and low-income countries, considering that there are more than one billion smokers in the world. However, currently, tobacco consumption is lower when compared to the beginning of the 2000s, demonstrating success in measures to combat drugs in several countries. Previous studies have shown that nicotine is the main active component of tobacco, being responsible for causing addiction in regular smokers. It was found that adolescence is a critical stage for the development of nicotine addiction, may cause future disorders. Due to the large number of diseases resulting from smoking, researchers have suggested conventional pharmacological therapies against smoking. However, due to the number of side effects and an unsatisfactory percentage of effectiveness, these methods still do not present a reliable alternative to the problem in question. The neuropeptide oxytocin (OXT), which is involved in social behaviors, has been shown to influence the system associated with the rewarding properties of drugs of abuse, known as mesocorticolimbic dopaminergic. So, OXT represents a therapeutic target for smoking cessation in adults and adolescents. Therefore, the objective of this work is to investigate how OXT interferes with the rewarding effects of nicotine in adult and adolescent mice, analyzing the consumption of nicotine in the free choice test between two bottles (TBC), as well as the patterns of locomotion and anxiety in open field (CA) test. Male and female mice of the Swiss strain were tested during the forty-seventh postnatal day (PN47) and ninety-seventh postnatal day (PN97) at TBC, for one week, being adolescents and adults, respectively. In this experiment, the animals received a nicotine solution at a dose of 10 μg/mL and intranasal administration of oxytocin at a dose of 100 µg/kg 1 hour before the start of TBC. These animals were also tested during the fortieth postnatal day (PN40) and ninetieth postnatal day (PN90) in CA, being adolescents and adults, respectively. In this experiment, the animals received a subcutaneous injection of nicotine at a dose of 0.5 mg/kg and intranasal administration of oxytocin at a dose of 100 µg/kg 1 hour before the onset of CA. With these methodologies we realized that OXT reduces nicotine consumption only in adolescent males, demonstrating that sex is an important variable to be considered. In addition, we found that OXT potentiates the psychostimulant effect and reverses the anxiogenic effect of nicotine in adolescents, as well as increasing the hypolocomotor and anxiogenic effect of nicotine in adults. Thus, it is possible to observe differences in the oxytocinergic system of adults and adolescents. To understand the mechanisms involved in nicotine addiction, we highlight the need for additional clinical and preclinical studies, in which age is relevant in this process, in addition to exploring the oxytocinergic system at different stages of life in healthy individuals or dependent on a drug of abuse and their social behavior