Varenicline prolonged exposure in rats: behavioral evaluation, central neurotransmitter levels, biochemical and histopathologic studies

Author(s)

Julia Zaccarelli Magalhães

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD)
• Defense date: 2016-12-09

Examining board members

Helenice de Souza Spinosa; Esther Lopes Ricci Adari Camargo; Milena Rodrigues Soares

• Advisor: Helenice de Souza Spinosa

Abstract

Varenicline is a synthetic chemical used for the smoking addiction treatment; it acts as an agonist of nicotinic cholinergic receptors, in particular, as a partial agonist of receptors α4β2 and α3β4 and as a full agonist of the α7 receptor. More studies about this substance are necessary, given that its clinical use is increasingly being applied to the treatment of addiction to a variety of abusive drugs. Moreover, there are few studies on vareniciline effects on behavior, cognition and the motor system. Thus, in this study the effects of prolonged (28-30 days) exposure of rats to varenicline were evaluated. It was analyzed the water and food consumption, the weight gain and the animal behavior, through open field, elevated plus maze, social interaction, stereotyped behavior, Barnes maze and passive avoidance tests. The neurotransmitter levels and their metabolites in different brain structures were measured and hematological, serum biochemistry, urinary evaluations and pathological and histological studies were carried out. We used three doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg orally (gavage). The results showed that prolonged exposure of rats to different doses of varenicline did not cause toxicity, since there were no changes in average weekly consumption of water or food nor body weight gain, which were measured weekly. As for behavioral assessments, there was a slight increase in overall activity in the open field as well as decreased time of social interaction. Varenicline was not able to change neurochemical, hematological, serum biochemical, urinary, pathology and histopathology parameters of rats. (AU)

• FAPESP's process: 15/05049-3 - Prolonged exposure of rats to varenicline: evaluation of the behavior, cerebral neurotransmitters, hematology, biochemistry and pathology
• Grantee: Julia Zaccarelli Magalhães
• Support Opportunities: Scholarships in Brazil - Master