RESUMO
Aluminum (Al) is a neurotoxicant agent implicated in several behavioral, neuropathological and neurochemical changes associated with cognitive impairments. Nevertheless, mechanisms of damage and safety concentrations are still very discussed. Thus, the main purpose of this study was to investigate whether two aluminum low doses were able to produce deleterious effects on cognition of adult rats, including oxidative stress in hippocampus and prefrontal cortex, two important areas for cognition. For this, thirty adult Wistar rats were divided into three groups: Al1 (8.3 mg/kg/day), Al2 (32 mg/kg/day) and Control (Ultrapure Water), in which all three groups received their solutions containing or not AlCl3 by intragastric gavage for 60 days. After the experimental period, the short- and long-term memories were assessed by the object recognition test and step-down inhibitory avoidance. After euthanizing, prefrontal cortex and hippocampus samples were dissected for Al levels measurement and evaluation of oxidative biochemistry. Only Al2 increased Al levels in hippocampal parenchyma significantly; both concentrations did not impair short-term memory, while long-term memory was affected in Al1 and Al2. In addition, oxidative stress was observed in prefrontal and hippocampus in Al1 and Al2. Our results indicate that, in a translational perspective, humans are subjected to deleterious effects of Al over cognition even when exposed to low concentrations, by triggering oxidative stress and poor long-term memory performance.
Assuntos
Cloreto de Alumínio/toxicidade , Alumínio/toxicidade , Hipocampo/efeitos dos fármacos , Síndromes Neurotóxicas , Córtex Pré-Frontal/efeitos dos fármacos , Alumínio/administração & dosagem , Alumínio/análise , Cloreto de Alumínio/administração & dosagem , Cloreto de Alumínio/análise , Animais , Hipocampo/química , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Memória de Longo Prazo/efeitos dos fármacos , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Ratos , Ratos WistarRESUMO
Understanding the impact of stress on cognitive processes, particularly decision-making, is crucial as it underpins behaviors essential for survival. However, research in this domain has yielded disparate results, with inconsistencies evident across stress-induction paradigms and drug administration protocols designed to investigate specific stress pathways or neuromodulators. Building upon empirical studies, this research identifies a multifaceted matrix of variables contributing to the divergent findings. This matrix encompasses factors such as the temporal proximity between stressors and decision tasks, the nature of stressors and decision contexts, individual characteristics including psychobiological profiles and affective states at the time of decision-making and even cultural influences. In response to these complexities, we propose a comprehensive model that integrates these relevant factors and their intricate interplay to elucidate the mechanisms governing decision-making during stressful events. By synthesizing these insights, our model not only refines existing paradigms but also provides a framework for future study designs, offering avenues for theoretical advancements and translational developments in the field of stress's impact on cognitive functions. This research contributes to a deeper understanding of the nuanced relationship between stress and decision-making, ultimately advancing our knowledge of cognitive processes under challenging conditions.
RESUMO
Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting.
RESUMO
[This corrects the article DOI: 10.1016/j.ibror.2019.07.216.].