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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 7
| Issue : 2 | Page : 72-78 |
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Exposure to aflatoxin and aggressive behavior among wistar albino rats
Ajibola Abdulrahamon Ishola
Department of Psychology, Faculty of the Social Sciences, University of Ibadan, Ibadan, Nigeria
| Date of Submission | 19-May-2020 |
| Date of Acceptance | 21-Jul-2020 |
| Date of Web Publication | 16-Sep-2020 |
Correspondence Address:
Ajibola Abdulrahamon Ishola
PMB Mellanby Hall, UI Post Office, Ibadan
Nigeria
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JNBS.JNBS_9_20
Background: Aflatoxin B1 (AFB1) contaminations of food have impact on human and animal health especially in sub-saharan Africa. However Animal model studies on the role of Aflatoxins in aggression behaviour is limited and this have implication for mental health and aggressive in children and emergent adults. Aims/Objective: The role of AFB1 in excessive territorial aggression behavior in Wistar rats was assessed. Material/Methods: Rodents in the experimental group (Group A, n = 6) were orally infused with AFB1 diluted in dimethylsulfoxide administered 0.3 mg/kg/day on days 1–12. Controls received distilled water similarly on days 1-12 days (Group B). For the observation, an intruder was introduced into the cage containing the residents who are experimental rats treated with aflatoxin and rats in the control treated with distilled water. Records of observations of territorial aggressive behaviors exhibited by the experimental and control rats toward the intruder were recorded. Each rat was given three trials of 5 min each. The study utilized the randomized blocked two-way ANOVA (factors timeline × treatment), followed by a post hoc analysis using Bonferroni correction to analyze the data, and statistical significance was set at P < 0.05. Results: Findings demonstrated that exposure to aflatoxin significantly influenced aggressive behavior among Wistar rats F (1, 322) = 29.89, P < 0.001, η2 = 0.09. Aflatoxin-treated animals significantly exhibited more aggressive behavior than animals treated with distilled water (Bonferroni = 4.04, P < 0.001). Exposure time to aflatoxin interacted with treatment to significantly influence aggressive behavior among Wistar rats F (1, 322) = 3.26, P < 0.001, η2 = 0.10. The mean comparison reveals that there was no significant difference in aggressive behavior of the aflatoxin-treated and distilled water-treated rats from days 1–7. However, significant differences were observed from the 8th day onward to the 12th day. Aggressive behavior increased by 10% as the chronic exposure increases more than 7 days. Conclusion: Aflatoxin-induced toxicity in rodents influenced aggression through exacerbation of neurocognitive decline and brain biochemical distortions leading to aggressive behavior.
Keywords: Aflatoxin toxicity, aggression-intruding behavior, neurocognitive, Wistar rats
How to cite this article:
Ishola AA. Exposure to aflatoxin and aggressive behavior among wistar albino rats. J Neurobehav Sci 2020;7:72-8 |
| Introduction | |  |
Aggression is an innate social trait that animals use to defend their own territory, maintain resources, and improve the probability of successful mating, thus an adaptive behavior. However, the behavior is no longer adaptive and is called maladaptive or pathologic aggression, when it is excessive, detrimental, disrupts the social order and its cost far outweighs its benefit. Unreasonable level of aggression in responses to incitement, indirect violence, or nonthreatening social cues has a detrimental effect on individuals and the community.[1] Unnecessarily high irritability and aggression are widely recognized as symptoms of many neuropsychiatric disorders, which can have an effect on the patients' quality of life and their caregivers.[1]
Aggressive behavior is also identified as symptomology of posttraumatic stress disorder, Alzheimer's disease, depression, schizophrenia, and substance abuse. Besides, excessive aggressive behavior poses a health risk to individuals and the community at large, and treatments are restricted and largely ineffective.[1] Nevertheless, multifactorial underlying causes of human aggression include policy, socioeconomic, cultural, medical, and psychological factors. It has also become clear that some forms of aggression, such as impulsive aggression (which occurs during emotional excitement and provocation), have an underlying neurobiology that researchers were only beginning to comprehend.[2] Intrinsic and extrinsic causes (for example, social and dietary effects, endocrine, and neurophysiological regulation mechanisms) may create, induce, and modulate an aggressive behavior. Both set of variables are related; in evolutionary adaptation processes, they undoubtedly played important roles.[2] Furthermore, in accordance with the modulated aggressiveness due to neurophysiological processes, it is usually unclear how dietary variables such as cholesterol, tryptophan, fatty acids, and neurotoxic substance, for example, aflatoxins, influenced aggressive behavior.
Aflatoxins belong to the family of mycotoxins; these are metabolites harmful to living creatures found in naturally occurring fungi. Aspergillus flavus, Aspergillus parasiticus, and aflatoxin B1 (AFB1) are among the known most effective teratogenic toxins, mutagens, and cancer-causing fungi.[3] High concentration of aflatoxins in animal feeds has been identified to trigger pathological issues in animals causing notable financial losses to farmers. Domestic animals were identified to be the most vulnerable to aflatoxins toxicity.[3] Aflatoxin is a leading food borne toxins in many of the animal organisms, and has been implicated in the etiology of human liver cancer through multiple clinical research studies,[4] and one of the most potent cancer-induced agents. In livestock, for instance, cow, chicken, or pig., household animals such as dogs, cats, and goats have been associated with aflatoxicosis. Congenital deformities and skeletal abnormalities in the intrauterine development of Wistar rats' babies were caused by exposure aflatoxins (aflatoxins).[4] The effect of toxicology on human and animal activity in the last four decades has grown in understanding and the neurosocial implications. For example, before birth, it has been implicated in the behavioral and intellectual deficit in geospatial cognitive capacities of Wistar rat weanlings exposed to AFB.[4] Parmer et al. (2016) have also implicated aflatoxins in the damage to neurobehavioral quality and synapses in chicks.
This study is premised on the growing concern that nutrition, which is essential for brain growth and functioning, is connected with aggression psychopathology.[5] There is a strong indication that nutrition can modulate greater levels of violent and aggressive behavior at the societal level based on studies from public health and neuroscience. In addition to major fatty acids in children, adolescents, and adults, the regulation of the dietary intake of vitamin and mineral was found to significantly diminished aggressive behaviors throughout the developmental milestones.[5] In studies on developmental milestones, early life nutrition was found to significantly modulate antisocial aggression and disruptive behavior at age 3 years and disruptive and hostile behavior during childhood and continues to play a major role in young adults' aggression (Liu et al., 2004).[5] This finding is further supported by the fact that dietary stimulation of antisocial behavior increased at age 3–17 years and increased aggressive behavior at age 23 years.[6] This trend broadly confirms the hypothesis that food intake plays a significant role in the development of and remediation of biological and neurobiological induced violent behavior and that at least part of the dietary intake affects aggressive behavior.[5]
Children in sub-Saharan Africa including Nigeria, early in life are exposed to aflatoxins right from the pre-natal stage through mothers' intake; preweaning period through breast milk, and after weaning through the consumption of maize, peanut and other foods high in aflatoxins.[7],[8] The bulk of these children are subject to elevated rates of aflatoxin during their lives, as most populations depend on subsistent farming and have little to no practices used to regulate the contamination of aflatoxins. Aflatoxin exposure has been associated with poor growth (underweight) and low immunity among children below age 5 years.[7],[8] Based on these, this study addresses the role of aflatoxins in aggressive behavior and its implication for aggressive behavior in humans exposed to its chronic dosage using the animal model.
Aflatoxins are currently being implicated in the aggressive behavior in animal models. Aggression is a being study in the pattern of territorial aggression. Territorial aggression is defined by aggressive acts or behaviour exhibited by an individual or a group in preventing strangers or animals of same specie trespassing through their territory, an action organized toward the protection of their territory; furthermore, the trait is established in animals that defend against and for intruders.[9] It is a significant part of intra-explicit challenge that can enable animals to access and hold restricted resources that improve their endurance and wellness.[10] Aggression is often utilized in the protection of region or offspring and in light of the danger of conspecific assault.[11],[12] Aggression additionally happens when animals vie for foods, water, and different assets important for endurance and proliferation.[13]
Excessive territorial aggressive behavior has been explained in terms of alteration in the functioning of a variety of neurological regions where violence has its biological roots. It has been proposed that biochemical activities at the various synapses interface acted in different ways to trigger the display or moderation of aggressive behaviour in animals. In any event, these sources have been linked to serotonin and glutamine neurotransmitters.[14],[15] Some researches have also shown that activities in the synapses can have an intensive impact on people's social characteristics. In particular, it was demonstrated that irregular synapse activities may trigger aggressive behavior.[15],[16],[17],[18] The serotonin inadequacy paradigm proposed that pleasant emotions, rational coordinated action, and a pleasant social image are exhibited once present in optimal quantity. Serotonin, a “happiness hormone,” as implicated, is said to affect the physiological environment, nerve cells, emotional function, and intellectual performance if inadequate may trigger aggression, negative feelings, and disruptive behavior.[14],[15] Aggression is also linked to disruptions in the cycle of glutamate/GABA-glutamine neurotransmitters. The synapse of glutamate helps strengthen the sensory focal system.[14],[15],[18] The way this neurotransmitter works is that it reduces discouragement and stabilizes emotional disposition and increased mental awareness. Glutamate infusion in animals' brains was found to increase their levels of aggression against other mice when incited.[15],[16],[17],[18] The overabundance of glutamate in the body has been emphatically connected to uneasiness, mood swings, hyperactivity, and disorganization that may trigger aggression in certain individuals. Aggression control is basic to diminished odds of an individual having psychological maladjustment.[15],[18]
Be that as it may, there is minimal distributed information on the neurobehavioral impacts of AFB on social conduct in animals or in humans. Studying the effects of aflatoxin on territorial aggression increases the understanding of its implication to human behavior; this is because the most animal model and human studies usually arrive at similar results. Identifying the possible effect accompanying the consumption of food products contaminated with aflatoxin unsuspectingly in the society is an effort toward combating the menace the toxin is causing in the society. Only one study of the functional effects of prenatal AFB exposure has been completed to date.[4] The present study, therefore, was conducted to determine the behavioral effects on social behavior in Wistar rats. This study is of benefit being that researchers rely on animal research to uncover fundamental aggression elements such as factors fueling, mental quest for violence, activation, and incentives toward gaining an understanding of the neurobiological processes underlying aggression. Through psychotherapeutic studies into aggression, pathological hostility is being identified and controlled.[2] Aggression has been correlated with disability in multiple cognitive functions, based on a decade of developments in the study and the capacity to suppress desires, modulate actions, and recognize, for example, the consequences of actions. They are assumed to have been attributed to neurological and brain function injury, violence, and impairments. Therefore, the need for understanding the neurobiological disability origins of violence in the brain and neuronal systems.[19],[20] The usefulness of this scientific endeavor includes expanded usage for therapeutic services (e.g., emergency, psychological, and critical care) reducing the cost of public safety, and of a larger interest to the criminal justice system relevant to neuroscience, psychiatry, and psychology, because they include a broad variety of adverse consequences of brain malfunction.[2] Thus, understanding the mechanism for aflatoxin-modulated aggression will provide information for treatment options and prevention of dietary-induced aggression.
Hypotheses
- Rats exposed to aflatoxin will significantly exhibit more territorial aggressive behavior than rats exposed to distilled water
- Rats exposed to aflatoxin treatment for longer days will significantly exhibit more territorial aggressive behavior than rats exposed to aflatoxin treatment for a shorter period.
| Methods | | |
Design
The design used in this study is a two-independent group randomized design.
Subjects
A total of 16 male albino rats (Rattus norvegicus) housed together in North Kent plastic breeding cages under constant and stable room temperature (24°C ± 2°C) and relative humidity of 50%–60% with a 12-h light–12 h dark cycle were used for the study. The rats were between 5 and 6 weeks old (Mage= 5.23 [standard deviation (SD) = 2.17] weeks). Food and water were available ad libitum. The rats were randomly selected into three groups comprising of; 6 males in the experimental group, 6 males in the control group and 4 males in the intruders groups for aggressive behavior observations. The rats weigh between 150–200g with a mean weight of 168.56 g (SD = 7.88g). The animals were humanely handled in accordance with the protocol for the Animal Care and Use Regulation Ethical Committee of the University of Ibadan, Ibadan, Nigeria.
Instruments
Distilled water administered orally as a placebo to the rats in the control group. Aflatoxin solution diluted with dimethyl sulfoxide (DMSO) was also administered orally to the experimental group. The blue, black, and red tail ring markers were used for easy identification of the rats in the control, experimental and intruder groups respectively. Experimental cages (16 North Kent Plastic cages [38 cm × 25 cm × 18 cm] were used to house the rats. Each cage has a top and floor made of stainless steel grid filled up with beddings). A Stopwatch was used for timekeeping while activities recordings were made on recording sheets.
Chemicals
AFB1 was purchased from Sigma Chemical Company, St. Louis, MO, USA. DMSO from the same organization was used to dissolve the AFB1 to a stock solution (25 mg/ml) and diluted to appropriate treatment concentrations. All the chemicals used, including solvents, were of high purity and analytical grade. Aflatoxin solution (0.3 mg/kg) for each of the rat was prepared daily and orally administered based on the weight of each rat (for the daily weighing using weighing balance of rats).
Behavioral test
Resident–intruder paradigm
This method involves a male rat, a system close to that in which animals are used and sometimes maintain and protect their territories, and serious fights, which are assumed to be natural fights, may occur in circumstances where inhabitants face an unknown male attacker on their territory and trigger aggressive behavior.[21] The scenario may include searching (patrolling), approach, investigation, threats fighting, chasing, dominant posturing, and urging inhabitants to behave aggression fully to intruders. The nature of the intruders, especially the size or hormone of the attackers and the previous experience of the occupant, differs between the attacking inhabitant and the adversary. The resident attacker design was also recognized as the intruding aggressive model. The frequency of aggressive behavior was included by de Almeida and Lucion.[22] It analyzed the frequency and duration of these behavioral actions and positions. For rats, the overall hostility level was determined as the maximum intensity number of tail rattle + chases + bites + cinches + rolling and tumbling fights + chasing + nasal contacts. The impact in displaying these seven aggressive behavioral elements of large individual differences was reduced in this approach.[23]
Procedure
The research started with the acquisition of 16 male albino rats weighing 180–200 g from the animal house of the Faculty of Veterinary Medicine, University of Ibadan. They were housed in North Kent plastic breeding cages in the veterinary animal research laboratory for 2 weeks to get acclimatized with the laboratory environment. The rats were randomly assigned into three groups of experimental, control and the intruder groups. They were all marked with tail rings in different colors for identification purpose. Data collection for this research took a duration of 24 days of alternate-day active treatment and observation making 12 days of active treatment. The rats were weighed on each day of treatment and administered with 0.3 mg/kg body weight of aflatoxin solution for the experimental group and distilled water for the control. The rats were allowed a period of 30 min before observations to ensure the onset of the effect of the treatment.
For the observation, an intruder was introduced into the cage containing each of the residents; the experimental (aflatoxin treated) and control (distilled water treated) at intervals. Four designated male rats that are neither in the control or experimental were utilized as intruders for aggressive behavior observations of the residents. Records of observations of territorial aggressive behaviors exhibited by the experimental and control rats toward the intruder were recorded. Each rat was given three trials of 5 min each. Average records of aggressiveness were taken for each rat as a record of aggressive behavior for the experimental period. The rats were properly fed after each experimental process for 24 h before the next experimental process. The treatment and observation process was repeated every other day for 12 days. The behavioral observation of interest for this research is the resident–intruder paradigm focusing on the behavior performed by the experimental rats as strongly dependent on the behavior performed by the intruder. Therefore, the following attributes of behaviors were recorded as aggression (tail rattle, chases, bites, cinches, rolling and tumbling fights, chasing, and nasal contacts) and also salient aggressive acts such as aggressive posture and sideway threats.
After treatment, the rats were observed for aggressive behavior. A statistical frequency table was drawn that consists of a tally box, number of territorial aggressive displays, frequency, and duration. Thereafter, a tally was ticked against the intruder rat exhibited aggressive cues toward the resident, this was done for each group (control and experimental), within the 0–5 min. The scores of each intruder male rat were gathered and at the end of the experiment for analysis.
Method of statistical analysis
All statistical analyses were performed using the software package SPSS (version 20). Behavioral parameters of the RI test were analyzed using randomized blocked two-way ANOVA (factors timeline × treatment), followed by a post hoc analysis using Bonferroni correction. Data are presented as mean + standard error of the mean. Statistical significance was set at P < 0.05.
| Results | | |
The study hypothesis stated that rats exposed to aflatoxin will exhibit more aggression than rats treated with distilled water was tested using the randomized factorial ANOVA and the result presented in [Table 1]. From the analysis, mean differences showed that aflatoxin-treated animals significantly exhibited higher aggressive behavior than animals treated with distilled water (F (1, 322) = 29.89, P < 0.001, η 2 = 0.09). The mean differences were significant (Bonferroni = 4.04, P < 0.001) (See [Table 2]). The result demonstrated that aggressive behavior increased by 8.5% with exposure to aflatoxin among the animals treated with aflatoxin compared to the control group. Based on this findings, the hypothesis thus stated that rats treated with aflatoxin will significantly exhibit more territorial aggressiveness than rats treated with distilled water is accepted. | Table 1: Summary factorial ANOVA table showing the influence exposure to aflatoxin on aggression behavior
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 | Table 2: Summary Bonferroni mean comparison analysis showing the mean difference between rats exposed to aflatoxin and those exposed to distilled water
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The second hypothesis stated that rats chronically exposed to aflatoxin for longer period of time will significantly display more aggressive behavior compared to Wistar rats treated with distilled water. This hypothesis was also tested using the factorial ANOVA, and the result is presented in [Table 1]. The result from [Table 1] shows that longer period or time of exposure to aflatoxin significantly influences aggressive behavior among Wistar rats F (1, 322) = 3.264, P < 0.001, η2 = 0.10 (See [Table 1]).
The result of mean comparison of the experimental to control group reveals that there was no significant difference in aggressive behavior of the aflatoxin-treated and distilled water-treated rats from days 1–7 (See [Table 3]). However, significant differences were observed between the aflatoxin-treated and distilled water-treated rats from the 8th day onward to the 12th day (See [Table 3]). A longer period of chronic exposure induced higher aggressive behavior in the aflatoxin-treated rats. The result demonstrated that aggressive behavior increased by 10%. The pattern of mean differences as the chronic exposure increases is presented in [Figure 1]. | Table 3: Bonferroni post hoc analysis showing mean differences based on treatment and period of days of exposure to aflatoxin
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 | Figure 1: Interaction graph showing the interaction between time of exposure and treatment to aflatoxin among Wister rats
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The line graph shows that longer period of chronic exposure induced higher aggressive behavior in the aflatoxin-treated rats from the 8th–12th days of the exposure. Based on this, the hypothesis stated that rats chronically exposing animals to aflatoxin for longer period of time will significantly influence the display of more aggressive behavior among Wistar rats treated with distilled water is thus accepted.
| Discussion | | |
The result demonstrated that aggressive behavior increased with exposure to aflatoxin among the animals treated with aflatoxin compared to the control group. It was presumed that the neurotoxic effect of aflatoxin impacted on the emotion regulating areas within hypothalamic and limbic brain areas that modulate aggression. It is believed that the ability to evaluate the situation appropriately and react accordingly when confronted with an intruder was greatly hampered by neurocognitive decline and distortions of the brain biochemicals, thus the excessive aggression. Thus, increasing levels of neurotoxicity were associated with corresponding aggression to the environment. This finding is in agreement with Kihara et al.[4] who have implicated prenatal exposure to AFB in behavioral and cognitive deficit in preweaning offspring and geospatial abilities in the postweaning offspring of Wistar rats. Furthermore, Parmer et al. (2016) implicated aflatoxin exposure in neurobehavioral toxicity and neurotransmitter disruption in chicks. Bbosa et al.[24] have established that the mycotoxins and metabolites, particularly their aflatoxins and other substances, interfere with healthy functioning by creating a chemical and oxidative stress that induces carcinogenicity, speeds up nerve cell death, and inhibits protein production. In the field of brain biochemistry; neurotoxic substance such as AFB1 have been identified to cause neurological symptoms such as neurocognitive impairement, altered sleep cycle, muscle tremor, convulsions, loss of memory, epilepsy, idiocy, loss of muscle coordination and depression resultant from neurotransmitter deficiencies.[24] In the same trend, Bahey et al.[25] have shown that the application of AFB1 causes multiple histopathological changes including cell degeneration, dilation of blood vascular and a significant decrease in frontal cortex thickness, and hippocampal pyramid cell layers. The amount of astrocyte production in the frontal cortex was significantly decreased without neuronal improvements. Stagkourakis et al.[26] clarify the role of aflatoxins in violence. Stagkourakis et al.[26] have shown that rodents with the highest levels of aggression are also shown to have more activated neurons in the ventral premotor cortex (PMv) of the hypothalamus, which is a significant emotional center of euphoria, sadness, and anger. Conversely, they are able to prevent an aggressive attack by deactivating PMv neurons. Brief PMv cell activation causing violence has been identified. They also reverse the “dominant/submissive” roles by deactivating PMv nerve cells in dominant rodents which made that the dominant rodents become submissive and vice versa. The potential to shift to dominant/submissive PMv area control means the ability to reduce or aggravate the neuropathic behavior of the aflatoxins. Recent studies have shown that bilateral PMV lesions in female rats significantly reduced the sexual behavior of females and maternal attacks against a male intruder.[27] Looking at these trends, it is demonstrated that diet high in aflatoxins disrupts and crosses the brain barrier and neurotransmitter activities leading to neurocognitive impairment and disturbances in brain biochemical interaction.[28],[29],[30] This has implications for aggressiveness and irritability in humans who consume food high in aflatoxin contamination after long exposure causing malnutrition, especially in children.[31]
| Conclusion | | |
Aggression behavior of resident Wistar rats in resident/intruder encounters was significantly influenced by prolonged duration of exposure to aflatoxin. The number of aggression attacks and the length of the attacks increased substantially over time. As identified, the neurotoxic effect of aflatoxin impacted on the emotion regulating areas within hypothalamic and limbic brain areas that modulate aggression. It is believed that the ability to evaluate the situation appropriately and react accordingly when confronted with an intruder was greatly hampered by neurocognitive decline and distortions of the brain biochemicals, thus the excessive aggression. This study recognizes the important role of biochemical factors in abnormal behavior. Toxic contamination of diet with aflatoxins has adverse, immediate, and long-term effects on aggressive behavior in rodents and by implication humans, especially children.
This current research provides a communication pathway that can provide a clearer understanding of the association between nutritional intake, central nervous system, and individual's psychological health status. Aside from the fact that aflatoxins lead to poor brain development and neurotoxicity of the central nervous system in childhood, it is established that it may be responsible for aggressiveness and irritability among children and infants. In increasing public health safety, there is a need to promote aflatoxin free and quality diet among children, especially those under-five so as to considerably decrease violent and aggressive activity at the community level. At the clinical level, a diet high in aflatoxins, for example, maize prepared meals, may trigger aggressiveness and irritability in patients with psychiatric and behavioral disorders. Thus, a quality diet low in aflatoxins can reduce costs and improve patient results during hospitalization. These findings may lead to a greater acceptance that neurotoxin intake affects the incidence of irritability and aggressiveness in rodents and possibly humans among health practitioners and health-care providers addressing aggression and psychological disorders.
Patient informed consent: There is no patient informed consent
Ethics committee approval: The research was a seminal paper for which no ethical is issued due to University being shut down due to Industrial action and Covid-19 pandemic
Lateef Olutoyin Oluwole (%28): involved in refining the conception of the work, the interpretation of data for the work and revising it critically for important intellectual content.
Christopher Goson Piwuna (%22): involved in refining the conception of the work, the interpretation of data for the work and revising it critically for important intellectual content.
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[Figure 1]
[Table 1], [Table 2], [Table 3]
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