Anti-HIV Drugs Nevirapine and Efavirenz Affect Anxiety-Related Behavior and Cognitive Performance in Mice Pedro R. T. RomaoJoelson C. LemosJeverson MoreiraGisele de Chaves • Morgana MorettiAdalberto A. CastroVanessa M. Andrade • Carina R. BoeckJoao QuevedoElaine C. Gavioli

Abstract Nevirapine (NVP) and efavirenz (EFV) belongto the class of anti-HIV drugs called non-nucleosidereverse transcriptase inhibitors (NNRTIs), commonly usedas part of highly active antiretroviral therapy (HAART).Although the HAART is able to bring down viral load toundetectable levels and restore immune function, theirprolonged use causes several adverse effects. It has beendemonstrated that both NVP and EFV are able to cross theblood–brain barrier, causing important central nervoussystem-related side effects. Thus, this study investigatedthe effects of chronic administration of EFV (10 mg/kg)and NVP (3.3 mg/kg) in mice submitted to two distinctseries of experiments, which aimed to evaluate: (1) theemotional behavior (elevated plus-maze, forced swimming,and open-field test) and (2) the cognitive performance(object recognition and inhibitory avoidance test) of mice.Our results demonstrated that EFV, but not NVP, reducedthe exploration to open arms in the elevated plus-maze test.Neither NVP nor EFV altered mouse behavior in the forcedswimming and open-field tests. Both drugs reduced therecognition index in the object recognition test, but onlyEFV significantly impaired the aversive memory assessedin the inhibitory avoidance test 24 h after training. Inconclusion, our findings point to a genuine anxiogenic-likeeffect to EFV, since it reduced exploration to open arms ofelevated plus-maze test without affecting spontaneouslocomotion. Additionally, both drugs impaired recognitionmemory, while only the treatment with EFV impairedsignificantly aversive memory.Keywords Antiretroviral drugsAlegre, Rua Sarmento Leite, 245-90050-170 Porto Alegre, RS, Efavirenz Nevirapine Elevated plus-maze test Object recognition task Inhibitory avoidance task Animal behaviorIntroductionThe highly active antiretroviral therapy (HAART) com-pletely changed the clinical evolution of HIV infection,reducing the morbidity and mortality among HIV-1 infec-ted patients and changing the incidence of neurologicalcomplications in acquired immunodeficiency syndrome(AIDS) patients (Sacktor et al. 2001). Nevirapine (NVP)and efavirenz (EFV) are antiretroviral drugs belonging topotent class of non-nucleoside reverse transcriptase inhib-itors (NNRTIs), commonly used as part of HAART