Rat Cerebellum Research Articles

The enriched environment prevents degeneration of cerebellum Purkinje cells layer of rats.

Neurodegeneration is characterized by loss of neurons causing changes that lead individuals to debilitating conditions; the most common of this condition is the Alzheimer's disease. It has been related that enriched environment (EE) induces experience‑dependent plasticity mechanisms, improving the performance of the animals in learning and memory tests. This study evaluated the effects of EE on histological parameters of the cerebellum in rats that received intracerebroventricular streptozotocin. In the standard environment, streptozotocin (STZ) promoted a significant increase between the gaps in the Purkinje layer of approximately 20%. On the other hand, in an enriched environment, the control result (EE) was similar to the result under streptozotocin effect (STZEE). In the standard environment (SE) group a 26% significant reduction in Purkinje cell density was observed under STZ presence. By analyzing the results of the density of Purkinje cells under the effect of streptozotocin in a standard environment (STZSE) against the density of the layer of Purkinje cells also under the effect of streptozotocin in an enriched environment (STZEE), a significant reduction of approximately 76% in density was observed of Purkinje cells in standard environment (STZSE), the mean number of Purkinje cells in enriched environments was not reduced, despite of STZ. According to the results, treatment with STZ and exposure to EE did not change the cerebellum general morphology/cytoarchitecture, hence was no significant difference in the layers thickness. These facts demonstrate that the enriched environment appears to protect the Purkinje cells layer of cerebellum from possible degeneration.

Effect of chronic maternal L-Glu intake during gestation and/or lactation on oxidative stress markers, AMPA Glu1 receptor and adenosine A1 signalling pathway from foetal and neonatal cerebellum.

L-Glutamate (L-Glu) is an amino acid present in the diet that plays a fundamental role in the central nervous system, as the main excitatory neurotransmitter participating in learning and memory processes. In addition, the nucleoside adenosine has a crucial role in L-Glu metabolism, by regulating the liberation of this neurotransmitter through four different receptors: A1, A2A, A2B and A3, which activate (A2A and A2B) or inhibit (A1 and A3) adenylate cyclase pathway. L-Glu at high concentrations can act as a neurotoxin and induce oxidative stress. The study of the oxidative stress correlated with an excess of L-Glu consumption during maternity is key to understand its effects on foetuses and neonates. Previous studies have shown that there is a change in the receptor levels in the brain of pregnant rats and their foetuses when mothers are administered L-Glu during gestation; however, its effect on the cerebellum is unknown. Cerebellum is known to be responsible for motor, cognitive and emotional functions, so its possible involvement after L-Glu consumption is an important issue to study. Therefore, the aim of the present work was to study the effect of L-Glu exposure during gestation and lactation on oxidative stress biomarkers and neurotransmitter receptors from the cerebellum of foetuses and neonates. After maternal L-Glu intake during gestation, oxidative stress was increased, as the ionotropic L-Glu receptors, and GluR1 AMPA subunit levels were altered in foetuses. A1 adenosine receptor suffered changes after L-Glu treatment during gestation, lactation or both, in lactating neonate cerebellum, while adenylate cyclase activity remain unaltered. Further studies will be necessary to elucidate the importance of L-Glu intake and its possible excitotoxicity in the cerebellum of Wistar rats during the pregnancy period and their involvement in long-term neurodegeneration.

Inhibiting cholinergic signalling in the cerebellar interpositus nucleus impairs motor behaviour.

The role of neuromodulators in the cerebellum is not well understood. In particular, the behavioural significance of the cholinergic system in the cerebellum is unknown. To investigate the importance of cerebellar cholinergic signalling in behaviour, we infused acetylcholine receptor antagonists, scopolamine and mecamylamine, bilaterally into the rat cerebellum (centred on interpositus nucleus) and observed the motor effects through a battery of behavioural tests. These tests included unrewarded behaviour during open field exploration and a horizontal ladder walking task and reward-based beam walking and pellet reaching tasks. Infusion of a mix of the antagonists did not impair motor learning in the horizontal ladder walking or the reaching task but reduced spontaneous movement during open field exploration, impaired coordination during beam walking and ladder walking, led to fewer reaches in the pellet reaching task, slowed goal-directed reaching behaviour and reduced reward pellet consumption in a free access to food task. Infusion of the muscarinic antagonist scopolamine on its own resulted in deficits in motor performance and a reduction in the number of reward pellets consumed in the free access to food task. By contrast, infusion of the nicotinic antagonist mecamylamine on its own had no significant effect on any task, except beam walking traversal time, which was reduced. Together, these data suggest that acetylcholine in the cerebellar interpositus nucleus is important for the execution and coordination of voluntary movements mainly via muscarinic receptor signalling, especially in relation to reward-related behaviour.

Neuroprotective effect of quercetin nanoparticles: A possible prophylactic effect in cerebellar neurodegenerative disorders

Memory deficit, anxiety, coordination deficit and depression are common neurological disorders attributed to aluminum (Al) buildup in the nervous system. Quercetin nanoparticles (QNPs) are a newly developed effective neuroprotectant. We aimed to investigate the potential protective and therapeutic effects of QNPs in Al induced toxicity in rat cerebellum. A rat model of Al-induced cerebellar damage was created by AlCl3 (100 mg/kg) administration orally for 42 days. QNPs (30 mg/kg) was administered for 42-days as a prophylactic (along with AlCl3 administration) or therapeutic for 42-days (following AlCl3 induced cerebellar damage). Cerebellar tissues were assessed for structural and molecular changes. The results showed that Al induced profound cerebellar structural and molecular changes, including neuronal damage, astrogliosis and tyrosine hydroxylase downregulation. Prophylactic QNPs significantly reduced Al induced cerebellar neuronal degeneration. QNPs is a promising neuroprotectant that can be used in elderly and vulnerable subjects to protect against neurological deterioration. It could be a promising new line for therapeutic intervention in neurodegenerative diseases.

Evaluation of The Ameliorative Effect of Green Tea Versus Berberine on Methyl Mercury Toxicity of Cerebellum in Adult Male Albino Rats, Histological & Immunohistochemical Study.

Evaluation of The Ameliorative Effect of Green Tea Versus Berberine on Methyl Mercury Toxicity of Cerebellum in Adult Male Albino Rats, Histological & Immunohistochemical Study.

Carica papaya Fruit Extract Protects the Cerebellum of Wistar Rats Against Acrylamide-Induced Oxidative Stress

Acrylamide is a water-soluble vinyl monomer produced industrially as an agent for the production of plastics and cosmetics, in waste water management as a flocculation agent, and naturally in fried, baked, and roasted foods, especially when heated beyond 120 °C. Acrylamide (AC) is associated with severe neurotoxic complications through the initiation of oxidative stress. Hence the use of Carica papaya (CP), a natural antioxidant, in protecting the cerebellum of Wistar rats against acrylamide-induced oxidative stress. Forty adult female Wistar rats (180-200 g) were divided into four groups (n=10): Control (1 mL distilled water), AC (25 mg/kg), CP (300 mg/kg), and CP+AC (300 mg/kg+25 mg/kg). All treatments were administered orally for 21 days. Thereafter, the rats were weighed, and neurobehavioural tests were done. The rats were sacrificed, while their cerebella were dissected out and preserved for oxidative stress, antioxidant markers, and histological and immunohistochemical studies. Data were analysed using analysis of variance at p<0.05. There was decreased body weight, locomotor activities, and forelimb grip strength in the AC-treated group compared with the control and other treated groups. Increased lipid peroxidation and nitric oxide levels, decreased glutathione (GSH) levels, and catalase, superoxide dismutase, and glutathione peroxidase activities in the AC-treated groups compared with the control and other treated groups. Histologically, degeneration, pyknosis, shrinking and loss of Purkinje neurons, reactive astrogliosis, and apoptosis occurred in the AC-treated group compared with the control and other treated groups. In conclusion, acrylamide induced oxidative stress in the rat cerebellum, and administration of CP fruit extract offered protection from its neurotoxic effects.

Influence of green tea on alcohol aggravated neurodegeneration of cortex, cerebellum and hippocampus of STZ-induced diabetic rats

The main aim of this study was to evaluate the cytotoxic effects of chronic alcohol consumption on various regions of diabetic brain and preventive role of GTE. Clinical, experimental and histopathological observations indicate chronic, excessive alcohol consumption aggravates the free radical-mediated oxidative and nitrosative stress in several tissues including brain. Treatment with Epigallocatechin gallate (EGCG) significantly reduced the levels of oxidative/nitrosative stress paradigms, increased glutathione (GSH) levels and enhanced the activities of antioxidant enzymes. Histopathology evaluation revealed the possible influence of EGCG in reversing alcohol exacerbated diabetes-induced damage in cortex, cerebellum and hippocampus of brain. Furthermore, these studies have provided evidence to show how EGCG can exactly occupy the position in functional sites of nNOS (neuronal nitric oxide synthase) and induce a conformational change, inhibition of enzymatic activity and prevention of neurodegeneration/necrotic changes of tissue, in comparison with the rosiglitazone and glibenclamide. To summarise, this research has offered useful information on the action of EGCG that would provide potential protection against ethanol exacerbated diabetic brain damageand additional evidence for the use of EGCG as a lead compound for drug discovery.

Oxidative brain and cerebellum injury in diabetes and prostate cancer model: Protective effect of metformin.

The body can host the spread of prostate cancer cells. Metastases from prostate cancer are more frequently seen in the brain, liver, lungs, and lymph nodes. A well-known antidiabetic drug, metformin, is also known to have antitumor effects. Our study focuses on the evaluation of potential metformin protective effects on brain and cerebellum damage in streptozotocin (STZ)-induced diabetic and Dunning prostate cancer models. In this investigation, six groups of male Copenhagen rats were created: control, diabetic (D), cancer (C), diabetic + cancer (DC), cancer + metformin, and diabetic + cancer + metformin. The brain and cerebellum tissues of the rats were taken after sacrifice. Oxidative stress markers including reduced glutathione level, lipid peroxidation, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase activities, reactive oxygen species, total oxidant and total antioxidant status, lactate dehydrogenase, xanthine oxidase, acetylcholinesterase activities, protein carbonyl contents, nitric oxide and OH-proline levels, sodium potassium ATPase, carbonic anhydrase, and glucose-6-phosphate dehydrogenase activities; glycoprotein levels including hexose, hexosamine, fucose, and sialic acid levels; and histone deacetylase activity as a cancer marker were determined. Oxidative stress markers were impaired and glycoprotein levels and histone deacetylase activity were increased in the D, C, and DC groups. Metformin therapy reversed these effects. Metformin was found to protect the brain and cerebellum of STZ-induced diabetic rats with Dunning prostate cancer from harm caused by MAT-Lylu metastatic cells.

Motor deficits are associated with increased glial cell activation in the hypothalamus and cerebellum of young rats subjected to cerebral palsy

Cerebral palsy (CP) is a syndrome characterized by a wide range of sensory and motor damage, associated with behavioral and cognitive deficits. The aim of the present study was to investigate the potential of a model of CP using a combination of perinatal anoxia and sensorimotor restriction of hind paws to replicate motor, behavioral and neural deficits. A total of 30 of male Wistar rats were divided into Control (C, n = 15), and CP (CP, n = 15) groups. The potential of the CP model was assessed by evaluating food intake, the behavioral satiety sequence, performance on the CatWalk and parallel bars, muscle strength, and locomotor activity. The weight of the encephalon, soleus, and extensor digitorum longus (EDL) muscles, and the activation of glial cells (microglia and astrocytes) were also measured. The CP animals showed delayed satiety, impaired locomotion on the CatWalk and open field test, reduced muscle strength, and reduced motor coordination. CP also reduced the weight of the soleus and muscles, brain weight, liver weight, and quantity of fat in various parts of the body. There was also found to be an increase in astrocyte and microglia activation in the cerebellum and hypothalamus (arcuate nucleus, ARC) of animals subjected to CP.

Pathophysiological aspects of neonatal anoxia and temporal expression of S100β in different brain regions.

The aim of this study was to investigate the temporal variations of S100β in the hippocampus, cerebellum and cerebral cortex of neonatal rats (Wistar strain) under anoxic conditions. Real-time PCR and western blotting techniques were used for gene expression and protein analysis. Animals were divided into two groups, a control group and an anoxic group, and further separated at different time points for analysis. After anoxia, S100β gene expression showed a significant peak in the hippocampus and cerebellum after 2 h, followed by a decline compared to the control group at other time points. The increased gene expression in these regions was also accompanied by an increase in S100β protein levels in the anoxia group, observable 4 h after injury. In contrast, S100β mRNA content in the cerebral cortex never exceeded control values at any time point. Similarly, the protein content of S100β in the cerebral cortex did not show statistically significant differences compared to control animals at any assessment time point. These results suggest that the production profile of S100β differs by brain region and developmental stage. The observed differences in vulnerability between the hippocampus, cerebellum and cerebral cortex may be attributed to their distinct developmental periods. The hippocampus and cerebellum, which develop earlier than the cerebral cortex, showed more pronounced effects in response to anoxia, which is supported by the gene expression and protein content in this study. This result reveals the brain region-dependent nature of S100β as a biomarker of brain injury.

Modulation of synapse-related gene expression in the cerebellum and prefrontal cortex of rats subjected to the contextual fear conditioning paradigm

The contextual fear conditioning (CFC) paradigm is the most productive approach for understanding the neurobiology of learning and memory as it allows to follow the evolution of memory traces of a conditioned stimulus and a specific context. The formation of long-term memory involves alterations in synaptic efficacy and neural transmission. It is known that the prefrontal cortex (PFC) exerts top-down control over subcortical structures to regulate behavioural responses. Moreover, cerebellar structures are involved in storing conditioned responses.The purpose of this research was to determine if the response to conditioning and stressful challenge is associated with alterations in synapse-related genes mRNA levels in the PFC, cerebellar vermis (V), and hemispheres (H) of young adult male rats. Four groups of Wistar rats were examined: naïve, CFC, shock only (SO), and exploration (EXPL). The behavioural response was evaluated by measuring the total freezing duration. Real-Time PCR was employed to quantify mRNA levels of some genes involved in synaptic plasticity. The results obtained from this study showed alterations in gene expression in different synapse-related genes after exposure to stressful stimuli and positioning to new environment. In conclusion, conditioning behavioural stimuli change the expression profile of molecules involved in neural transmission.

Non-Targeted Metabolic Profiling of Cerebellum in Spina Bifida Fetal Rats

Spina bifida, known more commonly as myelomeningocele, is a neural tube defect that results in herniation of the cerebellum through the foramen magnum into the central canal as part of the Chiari II malformation. Effects stemming from the herniated cerebellum and its metabolic profile have not been extensively studied. The objective of this study is to examine the metabolic effects of this disease on the cerebellum in utero through the utilization of a retinoid acid-induced Spina bifida rat model. Analysis of this model at mid-late (day 15) and term (day 20) of gestation in comparison to both non-exposed and retinoic acid-exposed non-myelomeningocele controls, the observed metabolic changes suggest that mechanisms of oxidative stress and energy depletion are at play in this neuro tissue. These notable mechanisms are likely to result in further damage to neural tissue as the fetus grows and the compressed cerebellum develops and herniates more due to myelomeningocele.

Neurotoxic Effect of the Insecticide Fipronil on the Cerebellum of Rats and the Possible Protective Role of Vitamin E (Light and Immunohistochemical Study)

Neurotoxic Effect of the Insecticide Fipronil on the Cerebellum of Rats and the Possible Protective Role of Vitamin E (Light and Immunohistochemical Study)

ЭФФЕКТЫ ВОЗДЕЙСТВИЯ ХРОНИЧЕСКОЙ АЛКОГОЛИЗАЦИИ И ГИПОДИНАМИИ НА ПОКАЗАТЕЛИ ДОФАМИНЕРГИЧЕСКОЙ СИСТЕМЫ НЕКОТОРЫХ ОТДЕЛОВ ГОЛОВНОГО МОЗГА КРЫС

Purpose of work. To determine the nature of changes in the content of dopamine and its metabolites in the cerebral cortex, hypothalamus and cerebellum of rats with chronic alcohol intoxication (CAI) against the background of physical inactivity (PI). Material and methods. The experiments were carried out on outbred white male rats weighing 180-220 g. Modeling of PI was carried out by placing rats in individual cages-pencil cases, limiting their mobility, for periods of 14 and 28 days. To simulate CAI, the animals were provided with an ethanol solution as the only source of fluid for 14 and 28 days. Determination of the content of the components of the dopaminergic system (tyrosine, 3,4-dioxyphenylalanine, dopamine, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and norepinephrine) was carried out using ion-pair high-performance liquid chromatography. Results. PI for 14 days is accompanied by signs of activation of the dopaminergic system in the hypothalamus and cerebral cortex of rats. With CAI for a period of 28 days, there are signs of a decrease in the activity of the dopaminergic system in the cerebral cortex. The combined effect of PI and CAI for 14 and 28 days leads to an increase in dopamine turnover in the cerebral cortex of rats. Conclusions. With the combined effect of CAI and PI, the most pronounced changes are observed in the cerebral cortex and are accompanied on the 14th day by an increase in the levels of HVA and DOPAC, and on the 28th day by an increase in the concentration of HVA.

Assessing the Location, Relative Expression and Subclass of Dopamine Receptors in the Cerebellum of Hemi-Parkinsonian Rats

Parkinson’s Disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons in the nigrostriatal pathway resulting in basal ganglia (BG) dysfunction. This is largely why much of the preclinical and clinical research has focused on pathophysiological changes in these brain areas in PD. The cerebellum is another motor area of the brain. Yet, if and how this brain area responds to PD therapy and contributes to maintaining motor function fidelity in the face of diminished BG function remains largely unanswered. Limited research suggests that dopaminergic signaling exists in the cerebellum with functional dopamine receptors, tyrosine hydroxylase (TH) and dopamine transporters (DATs); however, much of this information is largely derived from healthy animals and humans. Here, we identified the location and relative expression of dopamine 1 receptors (D1R) and dopamine 2 receptors (D2R) in the cerebellum of a hemi-parkinsonian male rat model of PD. D1R expression was higher in PD animals compared to sham animals in both hemispheres in the purkinje cell layer (PCL) and granule cell layer (GCL) of the cerebellar cortex. Interestingly, D2R expression was higher in PD animals than sham animals mostly in the posterior lobe of the PCL, but no discernible pattern of D2R expression was seen in the GCL between PD and sham animals. To our knowledge, we are the first to report these findings, which may lay the foundation for further interrogation of the role of the cerebellum in PD therapy and/or pathophysiology.

Tramadol Induces Histological Aberrations, Downregulation of Bcl-2 and Upregulations of GFAP, P53 Immunoexpression in the Cerebellum of the Male Albino Rat

Tramadol Induces Histological Aberrations, Downregulation of Bcl-2 and Upregulations of GFAP, P53 Immunoexpression in the Cerebellum of the Male Albino Rat

Epirubicin Treatment Induces Neurobehavioral, Oxido-Inflammatory and Neurohistology Alterations in Rats: Protective Effect of the Endogenous Metabolite ofTryptophan - 3-Indolepropionic Acid.

Epirubicin's (EPI) efficacy as a chemotherapeutic agent against breast cancer is limited by EPI's neurotoxicity associated with increased oxidative and inflammatory stressors. 3-Indolepropionic acid (3-IPA) derived from in vivo metabolism of tryptophan is reported to possess antioxidative properties devoid of pro-oxidant activity. In this regard, we investigated the effect of 3-IPA on EPI-mediated neurotoxicity in forty female rats (180-200g; five cohorts (n = 6) treated as follows: Untreated control; EPI alone (2.5mg/Kg); 3-IPA alone (40mg/Kg body weight); EPI (2.5mg/Kg) + 3-IPA (20mg/Kg) and EPI (2.5mg/Kg) + 3-IPA (40mg/Kg) for 28 days. Experimental rats were treated with EPI via intraperitoneal injection thrice weekly or co-treated with 3-IPA daily by gavage. Subsequently, the rat's locomotor activities were measured as endpoints of neurobehavioural status. After sacrifice, inflammation, oxidative stress and DNA damage biomarkers were assessed in rats' cerebrum and cerebellum alongside histopathology. Our results demonstrated that locomotor and exploratory deficits were pronounced in EPI-alone treated rats and improved in the presence of 3-IPA co-treatment. EPI-mediated decreases in tissue antioxidant status, increases in reactive oxygen and nitrogen species (RONS), as well as in lipid peroxidation (LPO) and xanthine oxidase (XO) were lessened in the cerebrum and cerebellum of 3-IPA co-treated rats. Increases in nitric oxide (NO) and 8-hydroxydeguanosin (8-OHdG) levels and myeloperoxidase MPO activity were also abated by 3-IPA. Light microscopic examination of the cerebrum and cerebellum revealed EPI-precipitated histopathological lesions were subsequently alleviated in rats co-treated with 3-IPA. Our findings demonstrate that supplementing endogenously derived 3-IPA from tryptophan metabolism enhances tissue antioxidant status, protects against EPI-mediated neuronal toxicity, and improves neurobehavioural and cognitive levels in experimental rats. These findings may benefit breast cancer patients undergoing Epirubicin chemotherapy.

Dexmedetomidine Protects Cerebellar Neurons against Hyperoxia-Induced Oxidative Stress and Apoptosis in the Juvenile Rat.

The risk of oxidative stress is unavoidable in preterm infants and increases the risk of neonatal morbidities. Premature infants often require sedation and analgesia, and the commonly used opioids and benzodiazepines are associated with adverse effects. Impairment of cerebellar functions during cognitive development could be a crucial factor in neurodevelopmental disorders of prematurity. Recent studies have focused on dexmedetomidine (DEX), which has been associated with potential neuroprotective properties and is used as an off-label application in neonatal units. Wistar rats (P6) were exposed to 80% hyperoxia for 24 h and received as pretreatment a single dose of DEX (5µg/kg, i.p.). Analyses in the immature rat cerebellum immediately after hyperoxia (P7) and after recovery to room air (P9, P11, and P14) included examinations for cell death and inflammatory and oxidative responses. Acute exposure to high oxygen concentrations caused a significant oxidative stress response, with a return to normal levels by P14. A marked reduction of hyperoxia-mediated damage was demonstrated after DEX pretreatment. DEX produced a much earlier recovery than in controls, confirming a neuroprotective effect of DEX on alterations elicited by oxygen stress on the developing cerebellum.

Protective Effect of Dexmedetomidine against Hyperoxia-Damaged Cerebellar Neurodevelopment in the Juvenile Rat.

Impaired cerebellar development of premature infants and the associated impairment of cerebellar functions in cognitive development could be crucial factors for neurodevelopmental disorders. Anesthetic- and hyperoxia-induced neurotoxicity of the immature brain can lead to learning and behavioral disorders. Dexmedetomidine (DEX), which is associated with neuroprotective properties, is increasingly being studied for off-label use in the NICU. For this purpose, six-day-old Wistar rats (P6) were exposed to hyperoxia (80% O2) or normoxia (21% O2) for 24 h after DEX (5 µg/kg, i.p.) or vehicle (0.9% NaCl) application. An initial detection in the immature rat cerebellum was performed after the termination of hyperoxia at P7 and then after recovery in room air at P9, P11, and P14. Hyperoxia reduced the proportion of Calb1+-Purkinje cells and affected the dendrite length at P7 and/or P9/P11. Proliferating Pax6+-granule progenitors remained reduced after hyperoxia and until P14. The expression of neurotrophins and neuronal transcription factors/markers of proliferation, migration, and survival were also reduced by oxidative stress in different manners. DEX demonstrated protective effects on hyperoxia-injured Purkinje cells, and DEX without hyperoxia modulated neuronal transcription in the short term without any effects at the cellular level. DEX protects hyperoxia-damaged Purkinje cells and appears to differentially affect cerebellar granular cell neurogenesis following oxidative stress.

Tramadol and Coffee Synergy Triggered Oxidative Stress, Altered Cerebellar Histomorphology and Behaviour in Rats

Tramadol intoxication with other substances has recently raised neurological concerns especially among youths in the society. The effects of tramadol and coffee on the cerebellum of Wistar rats were studied. Thirty adult Wistar rats (average weight of 180 g) were randomly assigned into six groups (n=6) as follows: Control, coffee (72.46 mg/kg), coffee (108.69 mg/kg), tramadol (2.86 mg/kg), tramadol (5.71 mg/kg) and coffee (72.46 mg/kg) + tramadol (2.86 mg/kg). The administrations were orally, and done once daily for twenty-eight consecutive days. On day 29, spontane-ous alternation in the T-maze was carried out, and the rats anaesthetized with ketamine hydrochloride (50 mg/kg intraperitoneally). Their blood were assayed for antioxidant, while the 10 % buffered formalin perfused brains were routinely processed with haematoxylin and eosin technique. Behavioural study showed significantly (p<0.05) increased spontaneous alternation in coffee (108.69 mg/kg), tramadol (5.71 mg/kg), and coffee (72.46 mg/kg) + tramadol (2.86 mg/kg) groups compared to the control. Catalase, superoxide dismutase and reduced glutathione levels were not different (p>0.05), while the malondialdehyde level was significantly (p<0.05) higher in the coffee (72.46 mg/kg) + tramadol (2.86 mg/kg) group compared to the control. Histological observations showed cerebellar cytoarchitectural alterations, including atrophy of the Purkinje cells in the coffee (108.69 mg/kg), tramadol (5.71 mg/kg), and coffee (72.46 mg/kg) + tramadol (2.86 mg/kg) groups compared to the control. In conclusion, co-administration of tramadol and coffee triggered free radicals, damaged the cerebellar tissues and caused a more deleterious effect on memory function than individual doses.