Nicotina modula a resposta de medo condicionado contextual em peixe-zebra

Abstract

Aversive conditions in a certain context trigger associative learning processes, which allow organisms to learn and anticipate potentially dangerous events. Exposure to conspecific alarm substance (CAS) has been used for modeling fear responses in zebrafish and the cholinergic system plays a role in cognitive functions. Thus, the goal of this study was to evaluate whether nicotine modulates contextual fear conditioning responses in zebrafish and a putative involvement of brain acetylcholinesterase (AChE) in associative learning. Fish were exposed to 1 mg/L nicotine and further transferred to experimental tanks in the absence or presence of 3.5 mL/L CAS for 5 min (training session). CAS was extracted by damaging epithelial cells into 10 mL distilled water using donor fish euthanized previously. After 24 hours, fish were placed to the same or to an altered context in the absence of CAS (post-training session). At training session, CAS increased freezing, erratic movements, and decreased the time spent in top area, while nicotine pretreatment abolished CAS effects on erratic movements. Nonetheless, nicotine/CAS group reintroduced to aversive context showed exacerbated freezing and reduced the number of entries in top area. Moreover, a decrease in distance traveled was observed in control, nicotine and nicotine/CAS groups at post-training session. Since the time spent in top area did not differ in animals retested in similar and altered contexts, this behavioral endpoint could reflect CAS-induced sensitization. Additionally, brain AChE activity increased in nicotine/CAS group reintroduced to the aversive context. Collectively, we demonstrate for the first time a positive modulation of nicotine on contextual fear conditioning in zebrafish and a putative involvement of cholinergic signaling in aversive responses.