Aggression is defined as hostile behavior that results in psychological damage, injury and even death among individuals. When aggression presents itself in an exacerbated and constant way, it can be considered escalating or pathological. The association between social stress and the emergence of exacerbated aggressiveness is common and is suggested to be interconnected through very complex neurobiological factors. For example, alterations in the expression of the dopaminergic receptors D1 and D2, reactive oxygen species (ROS) and the c-Fos protein in the cortex have been observed. Our objective was to analyze which factors are involved at the neurobiological level in the highly aggressive response of Swiss Webster adult male mice in a vivarium. In this work, we investigated the relationship among dopaminergic receptors, the production of ROS and the expression of c-Fos. Mice with exacerbated aggression were identified by the model of spontaneous aggression (MSA) based on the grouping of young mice and the regrouping of the same animals in adulthood. During the regrouping, we observed different categories of behavior resulting from social stress, such as (i) highly aggressive animals, (ii) defeated animals, and (iii) harmonic groups. To evaluate the dopaminergic system and the c-Fos protein, we quantified the expression of D1 and D2 dopaminergic receptors by Western blotting and fluorescence immunohistochemistry and that of the c-Fos protein by fluorescence immunohistochemistry. The possible production of ROS was also evaluated through the dihydroethidium (DHE) assay. The results showed that aggressive and subordinate mice showed a reduction in the expression of the D1 receptor, and no significant difference in the expression of the D2 receptor was observed between the groups. In addition, aggressive mice exhibited increased production of ROS and c-Fos protein. Based on our results, we suggest that exacerbated aggression is associated with social stress, dysregulation of the dopaminergic system and exacerbated ROS production, which leads to a state of cellular oxidative stress. The overexpression of c-Fos due to social stress suggests an attempt by the cell to produce antioxidant agents to reduce the toxic cellular concentration of ROS.

The aim of this work was to study the interaction of sulpiride with human serum albumin (HSA) and bovine serum albumin (BSA) through the fluorescence quenching technique. As sulpiride molecules emit fluorescence, we have developed a simple mathematical model to discriminate the quencher fluorescence from the albumin fluorescence in the solution where they interact. Sulpiride is an antipsychotic used in the treatment of several psychiatric disorders. We selectively excited the fluorescence of tryptophan residues with 290 nm wavelength and observed the quenching by titrating HSA and BSA solutions with sulpiride. Stern-Volmer graphs were plotted and quenching constants were estimated. Results showed that sulpiride form complexes with both albumins. Estimated association constants for the interaction sulpiride–HSA were 2.20 (±0.08) × 10⁴ M⁻¹, at 37 °C, and 5.46 (±0.20) × 10⁴ M⁻¹, at 25 °C. Those for the interaction sulpiride-BSA are 0.44 (±0.01) × 10⁴ M⁻¹, at 37 °C and 2.17 (±0.04) × 10⁴ M⁻¹, at 25 °C. The quenching intensity of BSA, which contains two tryptophan residues in the peptide chain, was found to be higher than that of HSA, what suggests that the primary binding site for sulpiride in albumin should be located next to the sub domain IB of the protein structure.

Stress is the body’s physiological reaction to a dangerous or threatening situation, leading to a state of alertness. This reaction is necessary for developing an effective adaptive response to stress and maintaining the body’s homeostasis. Chronic stress, caused mainly by social stress, is what primarily affects the world’s population. In the last decades, the emergence of psychological disorders in humans has become more frequent, and one of the symptoms that can be observed is aggressiveness. In the brain, stress can cause neuronal circuit alterations related to the action of hormones in the central nervous system. Leptin, for example, is a hormone capable of acting in brain regions and neuronal circuits important for behavioral and emotional regulation. This study investigated the correlation between chronic social stress, neuroendocrine disorders, and individual behavioral changes. Then, leptin and its receptors’ anatomical distribution were evaluated in the brains of mice subjected to a protocol of chronic social stress. The model of spontaneous aggression (MSA) is based on grouping young mice and posterior regrouping of the same animals as adults. According to the regrouping social stress, we categorized the mice into i) harmonic, ii) attacked, and iii) aggressive animals. For leptin hormone evaluation, we quantified plasma and brain concentrations by ELISA and evaluated its receptor and isoform expression by western blotting. Moreover, we verified whether stress or changes in leptin levels interfered with the animal’s body weight. Only attacked animals showed reduced plasma leptin concentration and weight gain, besides a higher expression of the high-molecular-weight leptin receptor in the amygdala and the low-molecular-weight receptor in the hippocampal region. Aggressive animals showed a reduction in the cerebral concentration of leptin in the hippocampus and a reduced high-and low-molecular-weight leptin receptor expression in the amygdala. The harmonic animals showed a reduction in the cerebral concentration of leptin in the pituitary and a reduced expression of the high-molecular-weight leptin receptor in the amygdala. We then suggest that leptin and its receptors’ expression in plasma and specific brain areas are involved in how individuals react in stressful situations, such as regrouping stress in MSA.

Comparative study of haloperidol (HPD), biperiden (BPD) and clonazepam (CNZ) interactions with human and bovine serum albumin was performed based on fluorescence quenching analysis. We used mathematical modeling comparing spectrofluorimetric data to obtain information on the possibility of competition among three drugs by sites binding. Results showed that the three drugs studied have high affinity for albumin and suggest the existence of two site classes in HSA for HPD and only one class for BPD and CNZ, in the range of concentrations tested for each drug. Among them, only HPD forms complex with HSA. Comparing normalized quenching plots suggested that the primary sites in HSA and BSA for HPD and CNZ are located at subdomain IB, whereas BPD would bind in the subdomain IIA. Considering the competition for binding sites in HSA, titrations of HPD-HSA complex by BPD and CNZ, as well as the titration of HSA solution containing CNZ titrated by BPD, show that although the three drugs do not compete with each other for binding sites, their interaction with HSA can cause conformational change in the protein, and to increase or decrease the accessibility to binding sites for other drug. This may mean alteration in the free plasma drug concentrations.