Vitamin D3 exerts immunomodulatory and memory improving properties in rats with lipopolysaccharide-induced inflammation.

INTRODUCTION: Vitamin D is a fat-soluble secosteroid, its primary function being regulation of calcium-phosphate homeostasis and maintenance of bone integrity and mineralization. Recently, pleotropic effects of this vitamin have been recognized, including an immunomodulatory role and involvement in normal brain development and functioning.

Pramipexole and tolcapone alleviate thermal and mechanical nociception in naive rats.

INTRODUCTION: Parkinson's disease (PD) is а neurodegenerative disorder characterized mainly by its motor symptoms. The non-motor symptoms including pain are increasingly recognized in the last few decades. Existing evidence suggests that the dopaminergic neurotransmission has an essential role in pain control. AIM: The aim of the present study was to investigate the antinociceptive effect of dopaminergic drugs pramipexole and tolcapone against chemical and thermal stimuli in naive rats. MATERIALS AND METHODS: Male Wistar rats divided into 8 groups (n=8): saline; diclofenac 25 mg/kg body weight (bw) (positive control); pramipexole 0.5; 1 and 3 mg/kg bw; tolacapone 5; 15 and 30 mg/kg bw. Paw pressure and plantar tests were performed. Paw withdrawal pressure and latent time were measured. Statistical analysis was done by SPSS 19. RESULTS: In the paw pressure test, pramipexole, in a dose of 1 and 3 mg/kg bw and tolcapone in a dose of 30 mg/kg bw, increased significantly the latency at 1, 2, and 3 hours compared to saline (p<0.05). In the plantar test, only the highest dose of pramipexole reached significance at 3 hours compared to the control rats (p<0.05). In contrast to pramipexole the three experimental groups with tolcapone markedly increased the latent time at 1 and 3 hours compared to saline (p<0.05). CONCLUSIONS: Pramipexole and tolcapone reduce mechanical and thermal nociception in naïve rats by enhancing dopaminergic neurotransmission at both spinal and supraspinal levels. In addition, tolcapone stimulates noradrenergic mediation which may contribute to its antinociceptive effect.

Dopaminergic agonist pramipexole improves memory and increases IL-10 production in LPS-challenged rats.

OBJECTIVES: A variety of cytokines are involved in cognitive functioning. Balance restoration between protective and degenerative neuro-inflammation is of great interest in newer therapeutic approaches. In the current study, we investigated the effect of pramipexole (PMX) on memory functions, hippocampal amyloid deposition, serum cytokines, and brain-derived neurotrophic factor (BDNF) levels in lipopolysaccharide (LPS) challenged-rats. MATERIALS AND METHODS: Male Wistar rats were divided into 5 groups (n=8): control (saline), lipoppolysacharide (LPS 250 mcg/kg bw), and experimental groups (LPS and PMX 0.5, 1, and 3 mg/kg bw). Learning and memory were assessed by the novel object recognition test (NORT), Y-maze, and step-through test. Immunological and histological assays were performed. RESULTS: In memory tasks, LPS-challenged rats showed reduction in the observed parameters. In NORT, PMX 1 mg/kg increased recognition index compared with controls, whereas the other two doses increased this index only against the LPS-control. In Y-maze, all doses of PMX significantly had increased alternation when compared with LPS. In the step-through test, only the lowest dose of PMX extended the latency compared with LPS. Histological examination revealed that PMX at doses of 0.5 and 1 mg/kg reduced amyloid deposition in the hippocampus. Interleukin (IL)-10 serum levels were elevated by 1 mg/kg PMX. Tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-ß1 serum levels remained under the detectable minimum in all experimental groups. PMX at all doses significantly decreased BDNF serum concentration. CONCLUSION: In rats with LPS-induced neuro-inflammation PMX improved hippocampal-dependent memory and exerted immuno-modulatory effects by increasing IL-10.

An experimental study on phytochemical composition and memory enhancing effect of Ginkgo biloba seed extract.

INTRODUCTION: The Ginkgo biloba L. tree is considered as one of the oldest species on Earth. It is known as a "living fossil" dating back approximately 200 million years. Both the leaves and seeds of this tree have been used for millennia in traditional Chinese medicine. AIM: To study the phytochemical profile of Gingko biloba seed extract (GBSE) and its memory enhancing effects. MATERIALS AND METHODS: Liquid chromatography with mass detection (LC-MS) was performed for phytochemical analyses of the extracts. For the in vivo experiments, male Wistar rats were divided randomly into 5 groups (n=8): saline; piracetam;  GBSE 50; 100, and 200 mg/kg b.w. Y-maze, T-maze, step-down passive avoidance and novel object recognition test (NORT) were performed. The observed parameters were: percentage of spontaneous alternations (% SA), working memory index, latency of reaction and recognition index, respectively. Statistical analysis was done using SPSS 19. RESULTS: LC-MS analysis showed the presence of the flavonoids quercetin, kaempferol and isorhamnetin (as aglycones), the ginkgolides A, B, C, J, and bilobalide. In Y-maze task, the groups treated with 50 and 100 mg/kg of GBSE significantly increased the % SA during the memory test compared to saline (p<0.05). In T-maze test, the three experimental groups with GBSE significantly increased the working memory index in comparison with that of the control group (p<0.05). In step-down test, the animals receiving 100 mg/kg b.w. GBSE, notably increased the latency during both retention tests (p<0.05 and p<0.01, respectively). In NORT, only the animals with the middle dose of GBSE ameliorated the recognition index when compared to saline (p<0.05). CONCLUSIONS: GBSE enhances spatial working memory, recognition memory, and short- and long-term recall in naïve rats due to the synergic effects of detected flavonoids and terpene lactones on brain functions. The brain structures involved are probably the hippocampus and prefrontal cortex.

Effects of Pramipexole on Learning and Memory Processes in Naïve and Haloperidol-challenged Rats in Active Avoidance Test.

BACKGROUND: Parkinson's disease (PD) is the second most common neurode-generative disease, usually detected by its motor symptoms. The non-motor symptoms, including cognitive deficits, have been of great interest to researchers in the last few decades. AIM: To assess the effect of pramipexole on learning and memory in naïve and haloperidol-challenged rats. MATERIALS AND METHODS: Male Wistar rats divided into 9 groups (n=8): naïve - saline, pramipexole 0.5; 1 and 3 mg/kg bw; Haloperidol groups - saline, haloperidol, haloperidol + pramipexole 0.5; 1 and 3 mg/kg bw. Two-way active avoidance test (TWAA) and activity cage were performed. The studied parameters were: number of conditioned and unconditioned responses, vertical and horizontal movements. Statistical analysis was done using SPSS 19. RESULTS: The naïve experimental groups significantly increased the number of conditioned responses during the tests for short- and long-term memory, compared with the saline groups (p<0.05). During the short-memory test only the animals with the lowest dose of PMX significantly increased the number of unconditioned responses whereas during the long-term memory test all experimental groups increased the number of escapes in comparison with the saline groups (p<0.05). Challenge dose of haloperidol attenuates learning and memory in pramipexol treated rats. Only the highest dose of pramipexol showed significant increase in conditioned and unconditioned responses compared with the haloperidol group (p<0.05). CONCLUSION: Pramipexole improves learning and memory in naïve rats by enhancing dopaminergic neurotransmission. This is probably not the only mechanism involved. This is confirmed by the decrease in learning and memory ability in rats with haloperidol-challenge.

Catechol-o-methyltransferase inhibitor tolcapone improves learning and memory in naïve but not in haloperidol challenged rats.

OBJECTIVES: Dopamine plays an important role in cognitive functions. Inhibition of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT) may have beneficial effects. Our aim was to assess the effect of COMT inhibitor tolcapone (TCP) on learning and memory in naïve and haloperidol-challenged rats. MATERIALS AND METHODS: Male Wistar rats were divided into 9 groups (n=8): naïve-saline, tolcapone 5; 15 and 30 mg/kg BW; haloperidol (HP) challenged-saline, haloperidol, haloperidol+tolcapone 5; 15 and 30 mg/kg BW. Two-way active avoidance test (TWAA), elevated T-maze, and activity cage were performed. Observed parameters were: number of conditioned responses (CR) and unconditioned responses (UCR), working memory index, and vertical and horizontal movements. RESULTS: Naïve rats with 30 mg/kg BW TCP had a significantly increased number of CR and UCR during the long-term memory test. The animals with 5 mg/kg BW TCP significantly increased the number of UCR during the two retention tests. In haloperidol-challenged rats, the three experimental groups decreased the number of CR and UCR during the learning session and the two memory tests, compared to the saline group. There was no significant difference between the HP-challenged rats treated with TCP and the haloperidol control group. All experimental naïve groups had significantly increased working memory index whereas none of the HP-challenged groups showed significant increase in this parameter. CONCLUSION: Our results demonstrate that in naïve rats tolcapone improves memory in the hippocampal-dependent TWAA task and spatial working memory in T-maze.

Study of antinociceptive effect of ketamine in acute and neuropathic pain models in rats.

BACKGROUND: Glutamate N-methyl-D-aspartate (NMDA) receptors are known for their importance in the perseverance of chronic neuropathic pain. Ketamine, an intravenous anesthetic agent, is a non-competitive blocker of NMDA receptors. Applied in anesthetic doses, ketamine has anti-nociceptive effects in various animal pain models. OBJECTIVES: The objective of this study was to investigate the anti-nociceptive effect of ketamine in acute and neuropathic pain models in rats. MATERIAL AND METHODS: To study the anti-nociceptive effect of ketamine on acute pain, 40 Wistar rats were divided into 5 groups (n = 8): control, positive control group and 3 experimental groups treated intraperitoneally (ip.) with 30 mg/kg bw, 40 mg/kg bw and 50 mg/kg bw ketamine, respectively. The anti-nociceptive effect was evaluated in hot plate, analgesy-meter and formalin tests. The model of neuropathic pain was induced by left sciatic nerve ligation. Twenty-four Wistar rats were divided into 3 groups (n = 8): sham-control group, model group and ketamine-treated group subsequently tested in hot plate and analgesy-meter tests. RESULTS: In the hot plate test, the rats treated with ketamine presented increased reaction latency at the 120th min and 180th min compared to the controls. In the analgesy-meter test, ketamine produced an antinociceptive effect at the 60th min compared to the controls. In the formalin test, the paw licking time across the early phase of testing was reduced in the rats treated with the 2 higher doses of ketamine. In a neuropathic pain model, ketamine increased the reaction latency at the 120th min and 180th min compared with the model group in the hot plate test. In the analgesy-meter test, in the ketamine-treated animals the paw withdrawal threshold increased at the 60th min compared with the model group. CONCLUSIONS: Our results suggest that ketamine produces peripheral anti-nociceptive effect in an acute pain model. Also, it relieves thermal and mechanical allodynia after 14 days of treatment in a neuropathic pain model.

Beneficial effect of commercial Rhodiola extract in rats with scopolamine-induced memory impairment on active avoidance.

Rhodiola rosea L., family Crassulaceae also known as Golden Root or Arctic root is one of the most widely used medicinal plants with effect on cognitive dysfunction, psychological stress and depression. The aim of the study was to examine the effect of a standardized commercial Rhodiola extract on learning and memory processes in naive rats as well as its effects in rats with scopolamine-induced memory impairment. MATERIALS AND METHODS: Sixty male Wistar rats were used in the study. The experiment was conducted in two series - on naive rats and on rats with scopolamine-induced model of impaired memory. The active avoidance test was performed in an automatic conventional shuttle box set-up. The criteria used were the number of conditional stimuli (avoidances), the number of unconditioned stimuli (escapes) as well as the number of intertrial crossings. RESULTS: The chemical fingerprinting of the standardized commercial Rhodiola extract was performed by means of nuclear magnetic resonance (NMR). Naive rats treated with standardized Rhodiola extract increased the number of avoidances during the learning session and memory retention test compared to the controls. Rats with scopolamine-induced memory impairment treated with Rhodiola extract showed an increase in the number of avoidances during the learning session and on the memory tests compared to the scopolamine group. The other two parameters were not changed in rats treated with the extract of Rhodiola in the two series. CONCLUSION: It was found that the studied Rhodiola extract exerts a beneficial effect on learning and memory processes in naive rats and rats with scopolamine-induced memory impairment. The observed effect is probably due to multiple underlying mechanisms including its modulating effect on acetylcholine levels in the brain and MAO-inhibitory activity leading to stimulation of the monoamines' neurotransmission. In addition the pronounced stress-protective properties of Rhodiola rosea L. could also play a role in the improvement of cognitive functions.

Antinociceptive and anti-inflammatory effects of Rhodiola rosea L. extract in rats.

BACKGROUND: Rhodiola rosea (golden root) is a unique phytoadaptagen with immunomodulatory, antioxidant, anti-inflammatory and antinociceptive activity. AIM: The aim of this study was to evaluate the antinociceptive and anti-inflammatory effects of the alcohol/water extract of Rhodiola rosea roots in rats. MATERIALS AND METHODS: Thirty male Wistar rats were used in the study. They were divided in 3 groups (n = 10), treated respectively with saline (controls), Rhodiola rosea extract 50 mg/kg bw and 100 mg/kg bw orally. The antinociceptive effect was evaluated using the hot-plate test, Randall-Sellito test and the formalin test. The hot-plate test evaluates the reaction time of rats which are dropped on a heated surface. The analgesy-meter test exerts a force increased at constant rate. In the formalin test we measured the total time spent in licking the injected paw during the early (0-10 min) and late phase (20-30 min) of test. To study anti-inflammatory effect the carrageenan-induced paw edema was used. The paw volume was measured plethysmometrically at 2, 3 and 4 hours. RESULTS: In the hot-plate test Rhodiola rosea increased in both doses the latency reaction compared with that in the controls. In analgesy-meter test Rhodiola rosea in a dose of 50 mg/kg showed a significant increase of pressure reaction compared with the controls. In the formalin test Rhodiola rosea in a dose of 100 mg/kg significantly decreased the paw licking time during the first phase. In the plethysmometer test Rhodiola rosea extract significantly reduced carrageenan-induced paw edema when compared with the saline-induced edema. CONCLUSION: The studied extract of Rhodiola rosea exhibited significant analgesic activity in all the pain models used--inhibition of thermal pain, mechanical hyperalgesia and formalin-induced pain behavior. Significant anti-inflammatory activity was observed from Rhodiola rosea extract in carrageenan induced paw edema in rats.

Effects of ketamine on memory and nociception in rats.

BACKGROUND: Ketamine is intravenous anaesthetic with NMDA-glutamate receptors mechanism of action. MATERIAL AND METHODS: Male Wistar rats were treated with saline (group A) or 10, 15 or 20 mg/kg of ketamine (groups B, C and D, respectively). For active avoidance test an automatic reflex conditioner was used. The observed variables were number of avoidances, escapes and intertrial crossings. Step-through and step-down passive avoidance tests were done with learning and memory retention test. Criteria for step-through test were latency of reactions of 180 sec in the light chamber. Criteria for step-down test were latency of reaction of 60 sec on the platform. The hot-plate test evaluates the reaction time of the rats dropped on a heated surface. The analgesy-meter test exerts a force increased at constant rate. RESULTS: In active avoidance test the controls increased the number of avoidances during learning and memory tests. Ketamine in all doses used increased the number of avoidances during learning and in memory test. Controls did not change the number of escapes, but the ketamine treated animals decreased it. The number of intertrial crossings was not changed by controls or ketamine-treated rats during learning and memory tests. In passive avoidance tests the controls and ketamine-treated rats increased the latency time during learning and memory retention tests. In hot-plate analgesic test and in analgesy-meter test the controls and ketamine-treated rats did not change the latency of reaction. CONCLUSION: The results suggest that ketamine improves learning and memory processes and has no analgesic effect in the doses applied.