RESUMO
Obsessive-compulsive disorder (OCD) is a chronic and debilitating illness that has been considered a polygenic and multifactorial disorder, challenging effective therapeutic interventions. Although invaluable advances have been obtained from human and rodent studies, several molecular and mechanistic aspects of OCD etiology are still obscure. Thus, the use of non-traditional animal models may foster innovative approaches in this field, aiming to elucidate the underlying mechanisms of disease from an evolutionary perspective. The zebrafish (Danio rerio) has been increasingly considered a powerful organism in translational neuroscience research, especially due to the intrinsic features of the species. Here, we outline target mechanisms of OCD for translational research, and discuss how zebrafish-based models can contribute to explore neurobehavioral aspects resembling those found in OCD. We also identify possible advantages and limitations of potential zebrafish-based models, as well as highlight future directions in both etiological and therapeutic research. Lastly, we reinforce the use of zebrafish as a promising tool to unravel the biological basis of OCD, as well as novel pharmacological therapies in the field.
Assuntos
Modelos Animais de Doenças , Transtorno Obsessivo-Compulsivo , Pesquisa Translacional Biomédica , Peixe-Zebra , Animais , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/genética , Humanos , Comportamento Animal/fisiologiaRESUMO
Functional changes in dopamine transporter (DAT) are related to various psychiatric conditions, including bipolar disorder (BD) symptoms. In experimental research, the inhibition of DAT induces behavioral alterations that recapitulate symptoms found in BD patients, including mania and depressive mood. Thus, developing novel animal models that mimic BD-related conditions by pharmacologically modulating the dopaminergic signaling is relevant. The zebrafish (Danio rerio) has been considered a suitable vertebrate system for modeling BD-like responses, due to the well-characterized behavioral responses and evolutionarily conservation of the dopaminergic system of this species. Here, we investigate whether GBR 12909, a selective inhibitor of DAT, causes neurobehavioral alterations in zebrafish similar to those observed in BD patients. Behaviors were recorded after a single intraperitoneal (i.p.) administration of GBR 12909 at different doses (3.75, 7.5, 15 and 30 mg/kg). To observe temporal effects on behavior, swim path parameters were measured immediately after the administration period during 30 min. Locomotion, anxiety-like behavior, social preference, aggression, despair-like behavior, and oxidative stress-related biomarkers in the brain were measured 30 min post administration. GBR 12909 induced prominent effects on locomotor activity and vertical exploration during the 30-min period. Hyperactivity was observed in GBR 30 group after 25 min, while all doses markedly reduced vertical drifts. GBR 12909 elicited hyperlocomotion, anxiety-like behavior, decreased social preference, aggression, and induced depressive-like behavior in a behavioral despair task. Depending on the dose, GBR 12909 also decreased SOD activity and TBARS levels, as well as increased GR activity and NPSH content. Collectively, our novel findings show that a single GBR 12909 administration evokes neurobehavioral changes that recapitulate manic- and depressive-like states observed in rodents, fostering the use of zebrafish models to explore BD-like responses in translational neuroscience research.
Assuntos
Mania , Peixe-Zebra , Animais , Humanos , Comportamento Animal , Encéfalo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Estresse Oxidativo , FenótipoRESUMO
Environmental contamination by pharmaceuticals from industrial waste and anthropogenic activities poses adverse health effects on non-target organisms. We evaluated the neurobehavioral and biochemical responses accompanying exposure to ecological relevant concentrations of atenolol (0, 0.1, 1.0, and 10 µg/L) for seven uninterrupted days in adult zebrafish (Danio rerio). Atenolol-exposed fish exhibited anxiety-like behavior, characterized by significant bottom-dwelling with marked reduction in vertical exploration. Atenolol-exposed fish exhibited marked increase in the duration and frequency of aggressive events without altering their preference for conspecifics. Biochemical data using brain samples indicated that atenolol disrupted antioxidant enzyme activities and induced oxidative stress. Exposure to atenolol markedly decreased ATP and AMP hydrolysis without affecting ADP hydrolysis and acetylcholinesterase (AChE) activity. Atenolol significantly upregulated tryptophan hydroxylase 1 (tph1) mRNA expression but downregulated brain-derived neurotrophic factor (bdnf) mRNA. Collectively, waterborne atenolol elicits aggressive and anxiety-like responses in adult zebrafish, accompanied by oxidative stress, reduced nucleotide hydrolysis, altered tph1 and bdnf mRNA expression, which may impact the survival and health of fish in aquatic environment.