Proposal of open field test as a model of varenicline pharmacokinetic study in rats

  • Julia Zaccarelli-Magalhães Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo
  • Thaisa Meira Sandini Faculdade de Ciências Farmacêuticas da Universidade de São Paulo
  • André Rinaldi Fukushima Universidade São Judas Tadeu
  • Helenice de Souza Spinosa Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo
Palavras-chave: Nicotinic Cholinergic Receptors, Open Field, Pharmacokinetic, Varenicline.


Varenicline is a medication used for smoking treatment that acts as a partial agonist for nicotinic cholinergic receptors α4β2 and α3β4 and as a total agonist of receptor α7 in the central nervous system. Pharmacokinetic is important information for medications that acts in the central nervous system. This kind of assay is commonly done by expensive and complex analytical techniques. Therefore, the aim of this study was to evaluate the possibility of using the open field test as a pharmacokinetic model for varenicline in male rats exposed to a single dose of varenicline. Male rats received a single dose orally (gavage) of three different concentrations of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg or water (control group). The open field observations were recorded 30 min, 1, 2, 4, 6, 24, 48, 72 h and 7 days after the administration of varenicline or water. The results showed alterations in locomotion and rearing frequencies, as well as in immobility time observed in open field, which is consistent with this drug’s plasma peak. Consequently, this behavioral test apparently can be considerate as a model for pharmacokinetic evaluation of varenicline.

Biografia do Autor

Julia Zaccarelli-Magalhães, Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo
Possui graduação em Bacharelado no curso de Ciências Biológicas da Universidade Presbiteriana Mackenzie (2014). Possui título de mestre em Ciências pela Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo (2016). Atualmente é aluna de doutorado no Programa de Patologia Experimental e Comparada na Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo.


BERNARDI, M.M.; PALERMO-NETO, J. Atividade geral: conceito e medidas. Psicologia, v.6, p.43-55, 1980.
CHOLERIS, E.; THOMAS, A.W.; KAVALIERS, M.; PRATO, F.S. A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field. Neuroscience & Biobehavioral Reviews , v.25, p.235-260, 2011.
CRUNELLE, C.L.; MILLER, M.L.; BRUIN, K.; BRINK, W.; BOOIJ, J. Varenicline increases striatal dopamine D2/3 receptor binding in rats. ‎Addiction Biology, v.14, p.500-502, 2009.
ERWIN, B.L.; SLATON, R.M. Varenicline in the treatment of alcohol use disorders. Annals of Pharmacotherapy, v.48, p.1445-1455, 2014.
FAESSEL, H.M.; BURSTEIN, A.H.; TROUTMAN, M.D. Lack of a pharmacokinetic interaction between a new smoking cessation therapy, varenicline, and digoxin in adult smokers. European Journal of Clinical Pharmacology, v.64, p.1101-1109, 2008.
FAESSEL, H.M.; OBACH, R.S.; ROLLEMA, H.; RAVVA, P.; WILLIAMS, K.E.; BURSTEIN, A.H. A review of the clinical pharmacokinetics and pharmacodynamics of varenicline for smoking cessation. Clinical Pharmacokinetics, v.49, p.799-816, 2010.
HALL, C.S. Emotional behavior in the rat: defecation and urination as measures of individual differences in the emotionality. Journal of Comparative Physiology, v.18, p.385-403, 1934.
HENCHOZ, Y.; BARD, B.; GUILLARME, D.; CARRUPT, P.; VEUTHEY, J.; MARTEL, S. Analytical tools for the physicochemical profiling of drug candidates to predict absorption/distribution. Analytical and Bioanalytical Chemistry, v.394, p.707–729, 2009.
HOOTEN, W.M.; WARNER, D.O. Varenicline for opioid withdrawal in patients with chronic pain: A randomized, single-blinded, placebo controlled pilot trial. Addictive Behaviors, v.42, p.69-72, 2015.
IIDA, M.; IIDA, H.; TAKENAKA, M.; TANABE, K.; IWATA, K. Preventive effect of varenicline on impairment of endothelial function in cerebral vessels induced by acute smoking in rats. Journal of Anesthesia, v.26, p.928-931, 2012.
MELLO, N.K.; FIVEL, P.A.; KOHUT, S.J.; CARROLL, F.I. Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotine+cocaine self-administration. Neuropsychopharmacology, v.39, p.1222–1231, 2014.
PRUT, L.; BELZUNG, C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. European Journal of Pharmacology, v.463, p.3– 33, 2003.
ROLLEMA, H.; SHRIKHANDE, A.; WARD, K.M.; TINGLEY II, F.D.; COE, J.W.; O'NEILL, B.T.; TSENG, E.; WANG, E.Q.; MATHER, R.J.; HURST, R.S.; WILLIAMS, K.E.; DE VRIES, M.; CREMERS, T.; BERTRAND, S.; BERTRAND, D. Pre-clinical properties of the α4β2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence. British Journal of Pharmacology, v.160, p.334-345, 2010.
SANDINI, T.M.; UDO, M.S.B.; REIS-SILVA, T.M.; BERNARDI, M.M.; SPINOSA, H.S. Prenatal exposure to integerrimine N-oxide impaired the maternal care and the pshysical and behavioral development of offspring rats. International Journal of Developmental Neuroscience, v.36, p.53–63, 2014.
TURNER, J.R.; CASTELLANO, L.M.; BLENDY, J.A. Nicotinic partial agonists varenicline and sazetidine-a have differential effects on affective behavior. Journal of Pharmacology and Experimental Therapeutics, v.334, p.665-672, 2010.
VALLE, F.P. Rats performance on repeated test in open-field as a function of age. Psychological Science, v.23, p.333-335, 1972.
VERRICO, C.D.; MAHONEY, J.J.; THOMPSON-LAKE, D.G.; BENNETT, R.S.; NEWTON, T.F.; DE LA GARZA, R. Safety and efficacy of varenicline to reduce positive subjectiveeffects produced by methamphetamine in methamphetamine-dependentvolunteers. International Journal of Neuropsychopharmacology, v.17, p.223–233, 2014.
WALSH, R.N.; CUMMINS, R.A. The open-field test: a critical review. Psychological Bulletin, v.83, p.482-504, 1976.
ZACCARELLI-MAGALHÃES, J.; MOREIRA, N.; SANDINI, T.M.; ABREU, G.R.; SANCHEZ-SARMIENTO, A.M.; RICCI, E.L.; FUKUSHIMA, A.R.; SPINOSA, H.S. Evaluation of prolongued exposure to varenicline in adult rats: heamatological, biochemical and anatomopathological studies. Basic & Clinical Pharmacology & Toxicology, v.122, p.305-309, 2018.
ZANIEWSKA, M.; MCCREARY, A.C.; STEFANSKI, R.; PRZEGALINSKI, E.; FILIP, M. Effect of varenicline on the acute and repeated locomotor responses to nicotine in rats. Synapse, v.62, p.935–939, 2008.
Como Citar
Zaccarelli-Magalhães, J., Meira Sandini, T., Rinaldi Fukushima, A., & de Souza Spinosa, H. (2018). Proposal of open field test as a model of varenicline pharmacokinetic study in rats. Revista Intertox De Toxicologia, Risco Ambiental E Sociedade, 11(3).