Substance use and substance use disorders in Africa: An epidemiological approach to the review of existing literature.

The relationship between man and substances that have abuse potentials, and whose use has been associated with the development or progression of substance use disorders has continued to evolve in terms of geography, economic implications, and time. History shows that local plants with psychoactive constituents can get exported worldwide through global travel, commerce, or even conquest. Time and globalization also change people's relationship with substances of abuse; hence, an area that was initially alien to certain substances might evolve to becoming a trafficking hub, and then a destination. A case in point is Africa where a rapidly increasing prevalence of substance use/abuse and substance use disorder among adolescents and young adults is putting enormous strain on the economy, healthcare system, and society at large. However, there appears to be a paucity of scientific literature and data on the epidemiology, risk assessment, and contributing factors to substance use and the development of substance use disorders across Africa. In this narrative review, we examine extant literature (PubMed, Google scholar, Medline) for information on the prevalence, trends, and influencers of substance use and the development of substance use disorders. This is with a view of understanding the determinants of substance use and factors that influence the development of substance use disorders in the region, and how this information can be channeled towards developing a comprehensive intervention and treatment program.

Nutrition, nutritional deficiencies, and schizophrenia: An association worthy of constant reassessment.

Schizophrenia is a mental health disorder that occurs worldwide, cutting across cultures, socioeconomic groups, and geographical barriers. Understanding the details of the neurochemical basis of schizophrenia, factors that contribute to it and possible measures for intervention are areas of ongoing research. However, what has become more evident is the fact that in targeting the neurochemical imbalances that may underlie schizophrenia, the type of response seen with currently available phamacotherapeutic agents does not provide all the answers that are needed. Therefore, the possible contribution of non-pharmacological approaches to schizophrenia management is worthy of consideration. In recent times, research is beginning to show nutrition may play a possibly significant role in schizophrenia, affecting its development, progression and management; however, while attempts had been made to examine this possible relationship from different angles, articles addressing it from a holistic point of view are not common. In this review, we examine existing scientific literature dealing with the possible relationship between nutrition and schizophrenia, with a view to elucidating the impact of diet, nutritional deficiencies and excesses on the aetiology, progression, management and outcome of schizophrenia. Secondly, the effect of nutritional supplements in prevention, as sole therapy, or adjuncts in schizophrenia management are examined.

Glutamate and depression: Reflecting a deepening knowledge of the gut and brain effects of a ubiquitous molecule.

The versatility of glutamate as the brain's foremost excitatory neurotransmitter and modulator of neurotransmission and function is considered common knowledge. Years of research have continued to uncover glutamate's effects and roles in several neurological and neuropsychiatric disorders, including depression. It had been considered that a deeper understanding of the roles of glutamate in depression might open a new door to understanding the pathological basis of the disorder, improve the approach to patient management, and lead to the development of newer drugs that may benefit more patients. This review examines our current understanding of the roles of endogenous and exogenous sources of glutamate and the glutamatergic system in the aetiology, progression and management of depression. It also examines the relationships that link the gut-brain axis, glutamate and depression; as it emphasizes how the gut-brain axis could impact depression pathogenesis and management via changes in glutamate homeostasis. Finally, we consider what the likely future of glutamate-based therapies and glutamate-based therapeutic manipulations in depression are, and if with them, we are now on the final chapter of understanding the neurochemical milieu of depressive disorders.

The potential toxicity of food-added sodium benzoate in mice is concentration-dependent.

Sodium benzoate (NaB) is a versatile food preservative that has also found some applications in the treatment of medical disorders. However, till date, its possible widespread effects on the body are not well studied. We examined the likely effect of diet-added NaB on weight/food intake, haematological parameters, neurobehaviour, antioxidant status, lipid profile and anti-inflammatory/apoptotic markers in mice. Animals were assigned randomly into 4 groups of 10 mice each. Groups included normal control (fed rodent chow) and three groups fed NaB at 125 (0.0125%), 250 (0.025% and 500 (0.05%) mg/kg of feed added to diet, respectively, for eight weeks. Body weight and food intake were assessed. At the end of the experimental period animals were euthanized, blood was then taken for the assessment of haematological, biochemical and inflammatory/apoptotic markers. At the lowest concentration, NaB diet increased body weight and food intake. Decrease in haematological cell counts and total antioxidant capacity were observed, whereas serum malondialdehyde levels and superoxide dismutase activity were increased across the three concentrations. Serum tumour necrosis factor-alpha and interleukin-10 decreased, whereas caspase-3 levels showed no significant difference. Lipid profile and biochemical indices of kidney and liver function were also affected by NaB diet. In conclusion, our findings suggest that NaB may be harmful if regulations regarding its limit of consumption are mistakenly or deliberately ignored. Therefore, it is advisable that regulations on quantities to be added to food be enforced.

Hazelnut Modulates Neurobehaviour and Ameliorates Ageing-induced Oxidative Stress, and Caspase-3-Mediated Apoptosis in Mice.

BACKGROUND: Organismal aging has been associated with deleterious effects in different body tissues and organs, including the brain. There have been reports from ancient medicinal scripts of the beneficial effects of nuts like hazelnut in preventing aging induced-brain atrophy and memory loss. OBJECTIVES: This study examined the potential beneficial effects of a diet supplemented with two different (Italian and Turkish) cultivars of hazelnut on the brain of aged mice. METHODS: Aged (24 months old) mice were randomly assigned into 7 groups of ten mice each. Mice were grouped as standard diet (SD) control, three groups of Turkish and three groups of Italian hazelnut incorporated into SD at 2, 4 and 8% respectively. Animals were fed standard or hazelnut diet for 8 weeks. On day 56, behaviours in the elevated plus maze, radial-arm maze, open field, and Y-maze paradigms were monitored and scored, following which animals were euthanized. The brains were removed, weighed and homogenized for the assessment of specific biochemical tests. RESULT: Results showed that hazelnut-supplemented diet was associated with significantly increased weight gain, with the Italian hazelnut being associated with greater weight gain. The hazelnut- supplemented diet also increased behavioural parameters such as horizontal locomotion and grooming, while it decreased rearing activity. Working-memory also improved significantly with both cultivars of hazelnut, while anxiety indices were reduced at lower concentrations of Italian, and higher concentrations of Turkish hazelnut. Both hazelnut varieties were associated with a reduction in acetylcholinesterase activity, superoxide dismutase activity, nitric oxide levels, caspase- 3 level, but increased dopamine level. CONCLUSION: Overall, hazelnut cultivars have beneficial effects on the brain in aged mice; suggesting a possible role in the prevention or management of age-related neurodegenerative changes.

Cucumeropsis mannii reverses high-fat diet induced metabolic derangement and oxidative stress.

Cucumeropsis mannii (CM) belongs to the melon family and is native to West Africa. There is a paucity of information on its medicinal or nutraceutical potential. Here, we examined the impact of CM in mice that were treated with a normal or a high fat diet (HFD). The CM extracts had a high levels of phenols, flavonoids, ascorbic acid and significant antioxidant activity. Treatment of mice with a HFD diet, led to the memory impairment. However, mice on HFD and received CM, despite increased food intake, showed a decrease in the body weight, locomotion, rearing, grooming, acetylcholinesterase activity and ?-amino butyric acid levels and anxiolysis. Also CM induced a reversal of HFD-induced changes in glucose levels, lipid peroxidation and super-oxide dismutase activity. These data show that CM leads to variable behavioural, biochemical and metabolic effects depending on the diet of animals.

Dietary Melatonin Protects Against Behavioural, Metabolic, Oxidative, and Organ Morphological Changes in Mice that are Fed High-Fat, High- Sugar Diet.

BACKGROUND: Metabolic syndrome is a complex pattern of disorders that occur jointly and is associated with an increased risk of cardiovascular and cerebrovascular disease. Therefore the need for more-efficient options of treatment has become imperative. OBJECTIVE: This study examined the effect of dietary-melatonin in the management of behavioural, metabolic, antioxidant, and organ changes due to high-fat/high-sugar (HFHS) diet-induced metabolic syndrome in mice. METHODS: Mice were randomly assigned into five groups of ten animals each. Groups were normal control [fed standard diet (SD)], HFHS control, and 3 groups of melatonin incorporated into HFHS at 2.5, 5, and 10 mg/kg of feed. Mice were fed for seven weeks, and body weight was assessed weekly. Open-field behaviours, radial-arm, and Y-maze spatial memory were scored at the end of the experimental period. Twenty-four hours after the last behavioural test, blood was taken for estimation of blood glucose levels after an overnight fast. Animals were then euthanised, and blood was taken for estimation of plasma insulin, leptin, and adiponectin levels, and serum lipid profile. The liver, kidneys, and brain were excised and processed for general histology, while homogenates of the liver and whole brain were used to assess oxidative stress parameters. RESULTS: Results showed that dietary melatonin (compared to HFHS diet) was associated with a decrease in body weight, food intake, and novelty-induced behaviours; and an increase in spatial-working memory scores. A decrease in glucose, insulin, leptin, and malondialdehyde levels; and an increase in adiponectin levels and superoxide dismutase activity were also observed. Histomorphological/ histomorphometric examination revealed evidence of organ injury with HFHS diet, and varying degrees of amelioration with melatonin-supplemented diet. CONCLUSION: In conclusion, dietary melatonin supplementation may have beneficial effects in the management of the metabolic syndrome.

The neurobehavioral implications of the brain and microbiota interaction.

In the past, microorganisms were not considered to be particularly important in brain development and functioning. However, recent evidence shows the existence of a bidirectional, and possibly multidimensional relationship between the body microbiota and the brain. The microbiota influence brain behavior in health or disease, by utilizing endocrine, neurocrine and immunologic signaling pathways. Also, the chemical mediators involved range from known neurotransmitters to small peptide molecules. Here, we discuss the evidence that currently exists in experimental animals and/or humans in support of the existence of a relationship involving the skin/gut microbiome, the brain, and behavior; and the mechanisms involved in such interactions. The implications of such interactions for shifts in behaviors, and the pathogenesis of behavioral and neurodegenerative disorders are also discussed. Finally, the possible clinical applications of deliberate manipulations of the microbiota composition and density for the management or prevention of behavioral and neurodegenerative disorders is discussed.

Brain Ageing, Cognition and Diet: A Review of the Emerging Roles of Food-Based Nootropics in Mitigating Age-related Memory Decline.

BACKGROUND: Age-related cognitive decline has been suggested to result from an increase in the brain neuron loss, which is attributable to continued derangement of the brain's oxidant/ antioxidant balance. Increased oxidative stress and a concomitant decrease in the brain's antioxidant defense system have been associated with functional senescence and organismal ageing. However, nature has configured certain foods to be rich sources of nootropic agents, with research showing that increased consumption of such foods or food ingredients may be protective against ageing-related memory decline. This knowledge is becoming increasingly valuable in an era when the boundary that separates food from medicine is becoming blurred. In this review, we examine extant literature dealing with the impact of ageing on brain structure and function, with an emphasis on the roles of oxidative stress. Secondly, we review the benefits of food-based antioxidants with nootropic effects and/or food-based nootropic agents in mitigating memory decline; with a view to improving our understanding of likely mechanisms. We also highlight some of the limitations to the use of food-based nootropics and suggest ways in which they can be better employed in the clinical management of age-related cognitive decline. CONCLUSION: While it is known that the human brain endures diverse insults in the process of ageing, food-based nootropics are likely to go a long way in mitigating the impacts of these insults. Further research is needed before we reach a point where food-based nootropics are routinely prescribed.

Cerebrovascular Disease in the Young Adult: Examining Melatonin's Possible Multiple Roles.

In the last decade or more, there have been reports suggesting a rise in the incidence of stroke in young adults. Presently, it appears that the risk factors associated with the cause of stroke in young adults remain relatively constant across different geographic regions of the world. Moreover, the endogenous rhythm of a neurohormone such as melatonin is known to play certain roles in the modulation of some of the risk factors that are associated with an increased risk of stroke in young people. Whereas animal studies have shown that melatonin plays diverse roles in stroke, only a limited number of human studies examined the roles of exogenous melatonin administration in the prevention of stroke, attenuation of neuronal damage, and improving outcome or well-being in stroke patients. In this review, first we summarize existing studies of stroke in the young adult and then provide insights on melatonin and stroke. Thereafter, we discuss the role of melatonin in models of stroke and how melatonin can be regulated to prevent stroke in young adults. Finally, we highlight the possible roles of melatonin in the management and outcome of stroke, especially in the young adult stroke population.

Nutraceuticals and Diet-based Phytochemicals in Type 2 Diabetes Mellitus: From Whole Food to Components with Defined Roles and Mechanisms.

BACKGROUND: Over the past decades, the development and use of an array of prescription medications have considerably improved the clinical management of type 2 diabetes mellitus and the quality of life of patients. However, as our knowledge of the associated risk factors and approaches to its management increases, the increasing roles of diet and the composition of the diet in the etiology and successful management of diabetes mellitus are being illuminated. Presently, a lot of attention is being given to nutraceuticals and certain phytochemicals that are integral parts of the human diet. It is believed that a clearer understanding of their roles may be crucial to 'non-invasive' or minimallyintrusive management, with regards to daily living of patients. In this review, an overview of nutraceutical components and phytochemicals that may be of benefit, or had been known to be beneficial in diabetes mellitus is given. Also, how the roles of such dietary components are evolving in the management of this disorder is highlighted. Lastly, the obstacles that need to be overcome before nutraceuticals can be considered as options for the clinical management of diabetes mellitus areconsidered. CONCLUSION: Despite studies that demonstrate their efficacy, no nutraceutical or food-derived compound has been formally adopted as a direct replacement for any class of antidiabetic drugs.

Ketamine-induced behavioural and brain oxidative changes in mice: an assessment of possible beneficial effects of zinc as mono- or adjunct therapy.

RATIONALE: We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. OBJECTIVES: Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively. Experiment 2 assessed the modulation of ketamine's effects following co-administration of zinc with haloperidol or olanzapine. METHODS: Male mice weighing 18-20 g each were used. Animals were pretreated with ketamine (except vehicle, zinc, haloperidol and olanzapine controls) for 10 days before commencement of 14-day treatment (day 11-24) with vehicle, zinc, haloperidol or olanzapine (alone or in combination). Ketamine injection also continued alongside zinc and/or standard drugs in the ketamine-treated groups. Zinc, haloperidol and olanzapine were administered by gavage. Treatments were given daily and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for estimation of glutathione, nitric oxide and malondialdehyde (MDA) levels. RESULTS: Ketamine increased open-field behaviours, nitric oxide and MDA levels, while it decreased working memory, social interaction and glutathione. Administration of zinc alone or in combination with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. CONCLUSION: Zinc may have the potential of a possible therapeutic agent and/or adjunct in the reversal of schizophrenia-like changes in behaviour and brain oxidative status.

Silymarin attenuates aspartame-induced variation in mouse behaviour, cerebrocortical morphology and oxidative stress markers.

OBJECTIVE: We assessed the impacts of silymarin co-administration on aspartame-induced changes in novelty-induced behaviours, memory, anxiety-related behaviours, cerebral antioxidant status and histomorphology in mice. METHOD: Six groups of mice were administered vehicle (distilled water), silymarin (25mg/kg), aspartame (at 160 or 320mg/kg), and silymarin (25mg/kg) co-administered with aspartame at 160 or 320mg/kg daily for 21days, via an oral cannula. Behaviours were assessed after the first and last dose of treatment. Animals were sacrificed thereafter. Brain homogenates were used to assess antioxidant status; while sections of the cerebral cortex were processed for routine histology. RESULT: Repeated co-administration of silymarin with aspartame resulted in significant suppression of horizontal locomotion and rearing, while grooming behaviour was enhanced; when compared to aspartame alone. Spatial working-memory showed significant improvement only after acute co-administration, while anxiety-related behaviours were reduced after repeated administration of both silymarin and aspartame. Cerebral cortical morphological integrity was better preserved, and astrocytic reactivity reduced with silymarin co-administration. Brain activity of superoxide dismutase and nitric oxide levels were decreased, while glutathione peroxidase activity was increased, when compared to levels seen with aspartame alone. CONCLUSION: The study shows that co-administration of silymarin with aspartame was associated with significant attenuation of central effects, when compared to administration of aspartame alone.

Monosodium glutamate-associated alterations in open field, anxiety-related and conditioned place preference behaviours in mice.

The present study investigated changes in behaviour associated with oral monosodium glutamate (a flavouring agent), using the open field, elevated plus maze and conditioned place preference (CPP) paradigms, respectively. Mice were assigned to two groups for CPP [monosodium glutamate (MSG)-naïve (n = 40) and MSG-pretreated (n = 40)] and two groups for open field (OF) and elevated plus maze (EPM) tests [n = 40 each], respectively. Animals in respective groups were then divided into four subgroups (n = 10) (vehicle or MSG (80, 160 and 320 mg/kg)). MSG-naïve mice were observed in the CPP box in three phases (pre-conditioning, conditioning and post-conditioning). Mice were conditioned to MSG or an equivalent volume of saline. The MSG pretreatment group received vehicle or respective doses of MSG daily for 21 days, prior to conditioning. Mice in the OF or EPM groups received vehicle or doses of MSG (orally) for 21 days, at 10 ml/kg. Open field or EPM behaviours were assessed on days 1 and 21. At the end of the experiments, mice in the OF groups were sacrificed and brain homogenates used to assay glutamate and glutamine. Results showed that administration of MSG was associated with a decrease in rearing, dose-related mixed horizontal locomotor, grooming and anxiety-related response and an increase in brain glutamate/glutamine levels. Following exposure to the CPP paradigm, MSG-naïve and MSG-pretreated mice both showed 'drug-paired' chamber preference. The study concluded that MSG (at the administered doses) was associated with changes in open field activities, anxiety-related behaviours and brain glutamate/glutamine levels; its ingestion also probably leads to a stimulation of the brain reward system.

Exogenous daytime melatonin modulates response of adolescent mice in a repeated unpredictable stress paradigm.

The immediate and short-term behavioural and physiological implications of exposure to stressful scenarios in the adolescent period are largely unknown; however, increases in occurrence of stress-related physiological and psychological disorders during puberty highlight the need to study substances that may modulate stress reactivity during a crucial stage of maturation. Seven groups of mice (12-15 g each) were administered distilled water (DW) (non-stressed and stressed controls), sertraline (10 mg/kg), diazepam (2 mg/kg) or one of three doses of melatonin (5, 10 and 15 mg/kg). Mice were exposed to 30 min of chronic mild stress (25 min of cage shaking, cage tilting, handling and 5 min of forced swimming in tepid warm water at 25 °C, in a random order) after administration of DW or drugs, daily for 21 days. Behavioural assessments were conducted on day 1 and day 21 (after which mice were sacrificed, blood taken for estimation of corticosterone levels and brain homogenates used for estimation of antioxidant activities). Administration of melatonin resulted in an increase in horizontal locomotion and self-grooming, while rearing showed a time-dependent increase, compared to non-stress and stress controls. Working memory improved with increasing doses of melatonin (compared to controls and diazepam); in comparison to setraline however, working memory decreased. A dose-related anxiolytic effect is seen when melatonin is compared to non-stressed and stressed controls. Melatonin administration reduced the systemic/oxidant response to repeated stress. Administration of melatonin in repeatedly stressed adolescent mice was associated with improved central excitation, enhancement of working memory, anxiolysis and reduced systemic response to stress.

Evidence of alterations in brain structure and antioxidant status following 'low-dose' monosodium glutamate ingestion.

OBJECTIVE: The study investigated the effects of low dose monosodium glutamate (MSG) on the brain, with a view to providing information on its effects on neuronal morphology and antioxidant status in mice. METHODOLOGY: Sixty male mice (20-22 g) were divided into six groups of ten animals each. Vehicle (distilled water), a standard (l-glutamate at 10mg/kg body weight) or MSG (10, 20, 40 and 80mg/kg body weight) were administered orally for 28days. Sections of the cerebrum, hippocampus and cerebellum were processed and stained using hematoxylin and eosin, examined under a microscope and captured images analysed. Plasma and brain levels of glutamate, glutamine, and antioxidants were assayed. Data obtained were analysed using descriptive and inferential statistics. RESULTS: MSG ingestion did not significantly alter body weight. Relative brain weight increased at 40 and 80mg/kg compared to vehicle. Histological and histomorphometric changes consistent with neuronal damage were seen in the cerebrum, hippocampus and cerebellum at 40 and 80mg/kg. Plasma glutamate and glutamine assay showed significant increase at 40 and 80mg/kg while no significant difference in total brain glutamate or glutamine levels were seen. Levels of brain superoxide dismutase and catalase decreased with increasing doses of MSG, while nitric oxide (NO) increased at these doses. CONCLUSION: The study showed morphological alterations consistent with neuronal injury, biochemical changes of oxidative stress and a rise in plasma glutamate and glutamine. These data therefore still support the need for cautious consideration in the indiscriminate use of MSG as a dietary flavor enhancer.

Caffeine's influence on object recognition and working-memory in prepubertal mice and its modulation by gender.

OBJECTIVE: This study investigated the effects of intraperitoneal injection of caffeine on Y-maze working-memory and novel object recognition (NOR) in prepubertal mice. METHODOLOGY: Y-maze spontaneous alternation and a novel object recognition test (consisting of acclimation, acquisition and test phases) were performed. Mice received a single dose of caffeine (10, 20, 40, 80 and 120mgkg(-1) i.p.) or vehicle, 30min before Y-maze exploration. For the NOR test, caffeine was given 30min before training and another dose 30min before test phase. RESULTS: NOR time (acquisition phase) increased significantly in males at all doses of caffeine and decreased in females at 10, 20 and 40mg/kg compared to vehicle; during the test phase, novel object exploration time decreased significantly in males and increased in females at 10 and 20mg/kg only to decrease again at 120mg/kg. Recognition index decreased in males and increased in females while, males showed poor discrimination between novel and familiar objects compared to vehicle; while females showed increased discrimination between novel and familiar object at 10, 20,40 and 80mg/kg and a decrease at 120mg/kg. Y-maze spontaneous alternation improved significantly in males at 10 and 40mg/kg and decreased at 20 and 120mg/kg in females. CONCLUSION: The findings suggest that acute caffeine injection improves non-spatial memory retention in female mice but not in males; spatial working-memory is however improved in males but not in females.

Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice.

This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.