Anxiolytic-like effect of Azadirachta indica A. Juss. (Neem, Meliaceae) bark on adult zebrafish (Danio rerio): participation of the Serotoninergic and GABAergic systems

Abstinence-induced anxiety is a common problem in drug abuse.2 This problem is associated when consumption is discontinued or abruptly reduced, with the occurrence of symptoms such as trembling, anxiety, insomnia, agitation, hypervigilance, irritability, piloerection and, sometimes, seizures.3 Benzodiazepines (GABA receptor agonists) and selective serotonin reuptake inhibitors (SSRIs) are the drugs of choice for the treatment of anxiety.2 SSRIs are also commonly used to treat depressive disorders.4 However, the chronic use of benzodiazepines causes tolerance, and abrupt treatment discontinuation may lead to withdrawal syndrome.5 On the other hand, the chronic use of SSRIs can result in considerable side effects,6 therefore the search for new compounds with anxiolytic and antidepressant properties that cause fewer adverse effects continues.7 Animal models are used for the assessment of new anxiolytic drugs. These pre-clinical models and screening tests support the studies, since clinical trials are expensive,8 especially regarding the central nervous system therapy.9 Currently, the zebrafish (Danio rerio) has been used in behavioral neuroscience, including research involving the brain and psychopharmacology.9 This vertebrate animal is considered a significant model in preclinical studies, because its genotype has 70% homology with mammalian neurotransmitter receptors.10