MPTP-lesioned Rats Research Articles

Neuroprotective Potential of HC070, a Potent TRPC5 Channel Inhibitor in Parkinson's Disease Models: A Behavioral and Mechanistic Study.

Transient receptor potential canonical 5 (TRPC5) channels are predominantly expressed in the striatum and substantia nigra of the brain. These channels are permeable to calcium ions and are activated by oxidative stress. The physiological involvement of TRPC5 channels in temperature and mechanical sensation is well documented; however, evidence for their involvement in the pathophysiology of neurodegenerative disorders like Parkinson's disease (PD) is sparse. Thus, in the present study, the role of TRPC5 channels and their associated downstream signaling was elucidated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP+) model of PD. Bilateral intranigral administration of MPTP and 24 h MPP+ exposure were performed to induce PD in the Sprague-Dawley rats and SH-SY5Y cells, respectively. MPTP led to behavioral anomalies and TRPC5 overexpression accompanied by increased calcium influx, apoptosis, oxidative stress, and mitochondrial dysfunctions. In addition, tyrosine hydroxylase (TH) expression was significantly lower in the midbrain and substantia nigra compared to sham animals. Intraperitoneal administration of potent and selective TRPC5 inhibitor, HC070 (0.1 and 0.3 mg/kg) reversed the cognitive and motor deficits seen in MPTP-lesioned rats. It also restored the TH and TRPC5 expression both in the striatum and midbrain. Furthermore, in vitro and in vivo studies suggested improvements in mitochondrial health along with reduced oxidative stress, apoptosis, and calcium-mediated excitotoxicity. Together, these results showed that inhibition of TRPC5 channels plays a crucial part in the reversal of pathology in the MPTP/MPP+ model of Parkinson's disease.

Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease dementia in rats.

Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200mg/kg body weight) was administered orally starting 3days prior to MPTP injection and was continued for 20days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators-COX-2, iNOS-as well reduced the levels of cytokines-interleukins (IL)-IL-1β, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.

Ceftriaxone attenuates glutamate-mediated neuro-inflammation and restores BDNF in MPTP model of Parkinson’s disease in rats

The present study is designed to investigate the role of glutamate transporter in neuroprotection of ceftriaxone against MPTP induced PD animal model. Young male Wistar rats were subjected to intra-nigral administration of MPTP for the induction of Parkinson’s disease. Glutamate modulators like ceftriaxone (CFX), Memantine (MEM) and Dihydrokainate (DHK) were administered to MPTP-lesioned rats. Different behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical parameters were measured. Intranigral administration of MPTP showed significant impairment of motor behavior and marked increase in inflammatory mediators and oxidative stress parameters in rats. In addition, MPTP also produced significant decrease in brain-derived neurotrophic factor (BDNF) in striatum of rats. However, chronic administration of ceftriaxone (200mg/kg) has shown significant improvement in motor behavioral deficits and oxidative damage. In addition, Ceftriaxone also attenuated the marked increase of NFκB, TNF-α and IL-1β in MPTP treated rats thus, conferring its neuro-inflammatory property. Further, Ceftriaxone significantly restored the decreased activity of BDNF in striatum of MPTP treated rats. Moreover, pre-treatment of memantine (20mg/kg) with sub-therapeutic dose of ceftriaxone (100mg/kg) potentiated the protective effect of ceftriaxone. Furthermore, intra-nigral injection of DHK (200 nmol) with lower dose of ceftriaxone (100mg/kg) reversed the protective effect of ceftriaxone in MPTP treated rats. The present study concluded that ceftriaxone produce beneficial effect against MPTP induced PD like symptoms rats through glutamatergic pathways.

Effects of ceftriaxone on the behavioral and neuronal changes in an MPTP-induced Parkinson's disease rat model.

Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD) and treatment with drugs modulating glutamatergic activity may have beneficial effects. Ceftriaxone has been reported to increase glutamate uptake by increasing glutamate transporter expression. The aim of this study was to determine the effects of ceftriaxone on working memory, object recognition, and neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. MPTP was stereotaxically injected into the substantia nigra pars compacta (SNc) of male Wistar rats. Then, starting the next day (day 1), the rats were injected daily with either ceftriaxone (200 mg/kg/day, i.p.) or saline for 14 days and underwent a T-maze test on days 8-10 and an object recognition test on days 12-14. MPTP-lesioned rats showed impairments of working memory in the T-maze test and of recognition function in the object recognition test. The treatment of ceftriaxone decreased the above MPTP-induced cognitive deficits. Furthermore, this study provides evidence that ceftriaxone inhibits MPTP lesion-induced dopaminergic degeneration in the nigrostriatal system, microglial activation in the SNc, and cell loss in the hippocampal CA1 area. In conclusion, these data support the idea that hyperactivity of the glutamatergic system is involved in the pathophysiology of PD and suggest that ceftriaxone may be a promising pharmacological tool for the development of new treatments for the dementia associated with PD.

Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson's disease: a comparison study of mononuclear and mesenchymal stem cells.

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development.

Blockade of metabotropic glutamate receptors inhibits cognition and neurodegeneration in an MPTP-induced Parkinson's disease rat model

Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD). Metabotropic glutamate receptor subtype 5 (mGluR5) modulates glutamatergic transmission and thus has been proposed as a potential target for neuroprotective drugs. The aim of this study was to determine the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), an mGluR5 antagonist, on working memory, object recognition, and neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. Male Wistar rats were stereotaxically injected with MPTP into the substantia nigra pars compacta (SNc). Starting 1day after lesioning (day 1), the rats were treated daily with MPEP (2mg/kg/day, i.p.) for 14days and rats underwent a T-maze test on days 8–10 and an object recognition test on days 12–14. MPTP-lesioned rats showed impairments of working memory in the T-maze test and of recognition function in the object recognition test and both effects were prevented by MPEP treatment. Furthermore, MPTP lesion-induced dopaminergic degeneration in the nigrostriatal system, microglial activation in the SNc, and cell loss in the hippocampal CA1 area were all inhibited by MPEP treatment. These data provide support for a role of mGluR5s in the pathophysiology of PD and suggest that MPEP is a promising pharmacological tool for the development of new treatments for dementia associated with PD.

Effects of MK-801 on recognition and neurodegeneration in an MPTP-induced Parkinson's rat model

Several years after the diagnosis of Parkinson's disease (PD), 20–30% of PD patients develop dementia, known as Parkinson's disease dementia (PDD), the features of which include impairment of short-term memory and recognition function. Hyperactivation of the glutamatergic system is implicated in the neurodegeneration seen in PD. The aim of this study was to determine the effects of MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, on short-term memory and object recognition in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat animal model. MPTP was injected stereotaxically into the substantia nigra pars compacta (SNc) of male Wistar rats, then, starting 1 day later (day 1), the rats were injected daily with MK-801 (0.2mg/kg/day, i.p.) and rats underwent a bar test on days 1–7, a T-maze test on days 8–10, and object recognition test on days 12–14. On day 1, the animals showed motor dysfunction, which recovered to control levels on day 7. MPTP-lesioned rats showed impairment of working memory in the T-maze test and of recognition in the object recognition test, both of which were prevented by MK-801 treatment. Furthermore, MPTP lesion-induced dopaminergic degeneration in the nigrostriatal system, microglial activation in the SNc, and cell loss in the hippocampal CA1 area were all improved by MK-801 treatment. These results suggest that NMDA receptors are involved in PD-related neuronal and behavioral dysfunction.

Effects of d-cycloserine on MPTP-induced behavioral and neurological changes: Potential for treatment of Parkinson's disease dementia

Glutamatergic dysfunction has been implicated in the neurodegeneration seen in Parkinson's disease (PD). Sub-chronic intraperitoneal injection with d-cycloserine (DCS), a partial agonist at the glycine binding site of the N-methyl- d-aspartate (NMDA) receptor, at dosages of 30, 100, or 200 mg/kg/day, was used to evaluate the role of NMDA receptors in neuronal and behavioral changes in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. Starting one day after intra-nigral infusion of MPTP, transient disturbance of motor function in the rotarod test was observed. This impairment spontaneously recovered to control levels 6 days after MPTP lesioning and DCS treatment facilitated recovery. MPTP lesioning also caused deficits in working memory and anxiety-like behavior in the T-maze and elevated plus-maze tests, respectively. Further, object recognition was disrupted in MPTP-lesioned rats, and interleukin-2 levels in the striatum, amygdala, and non-prefrontal cortex were increased, both changes being restored by DCS treatment. Furthermore, MPTP lesion-induced dopaminergic degeneration, microglial activation, and cell loss in the hippocampal CA1 area were all improved by DCS treatment. These results suggest that NMDA receptors are involved in PD-related neuronal and behavioral dysfunctions and that DCS may have clinical potential in the treatment of dementia associated with PD.

MPTP-induced dopaminergic degeneration and deficits in object recognition in rats are accompanied by neuroinflammation in the hippocampus

Emotional changes, impairment of object recognition, and neuroinflammation are seen in Parkinson's disease with dementia (PDD). Here, we show that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the rat substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, microglial activation in the SNc and hippocampus, and cell loss in the hippocampal CA1 area. With regard to behavior, an increase in anxiety-like behavior and impairment of object recognition were observed during the fourth week after MPTP lesioning. The behavioral changes were not caused by motor impairment, since the rats had already recovered from MPTP-induced catalepsy before the tests were performed. These findings show that MPTP-induced neuroinflammation and its consequences, for example, microglial activation and cell loss in the hippocampus, may be involved in dopaminergic degeneration-related behavioral deficits and suggest that, in addition to the dopaminergic system, the limbic system may also participate in the pathophysiology of PDD. MPTP-lesioned rats are therefore proposed as a useful tool for assessing the ability of pharmacological agents to prevent recognition deficits in PDD.

MPTP-induced Animal Model of Parkinson's Disease Dementia: There are Species Differences

Event Abstract Back to Event MPTP-induced Animal Model of Parkinson's Disease Dementia: There are Species Differences Shih Chun Ho1* and Ying Jui Ho1 1 Chung Shan Medical University, School of Psychology, Taiwan Animals treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are used as models of Parkinson's disease. This study analyzed changes of motor, anxiety, recognition, and learning in MPTP-lesioned Wistar rats and C57BL/6 mice, which was intended to establish a useful model of Parkinson's disease dementia. MPTP was bilaterally infused into the substantia nigra pars compacta (SNc) of male Wistar rats. Starting one day after the MPTP lesion, the rats were subjected to a battery of behavioral tests for measuring motor function in the rotarod, anxiety level in the elevated plus-maze (EPM), learning and working memory in the T-maze, and recognition in the object recognition task. Male C57BL/6 mice receiving intraperitoneal injection of MPTP were subjected to a battery of behavioral tests for measuring motor function in the open field, anxiety level in the EPM, learning function in the active avoidance task (AAT), and recognition in the object recognition task. Both rats and mice showed motor deficits in the rotarod and open field test, respectively, one day after MPTP lesioning. However, such impairments in the rats were reversed to control levels 7 days after the MPTP lesion, which were assessed by measuring percentage of movement time on the rotarod. Similarly, analyzing total distance and movement time in the open field, motor impairments of the mice were also reversed to control levels 11 days after the MPTP lesion. Decreased exploration time to novel objects in the object recognition test was observed in both rats and mice treated by MPTP. MPTP lesion suppressed open arm time and open arm entry in the EPM test in rats, but not in mice. In addition, MPTP-lesioned rats showed lowered correct responses in the T-maze test. However, no effect of MPTP lesion was found on learning ability in the AAT in mice. In summary, MPTP lesion in rats caused deficits in motor, anxiety, recognition, and learning ability. MPTP-treated mice showed impairments in movement and recognition, but not in anxiety level and learning ability. These results provide evidence for taking the species differences into account when animal models for studying symptoms of early phase of Parkinson's disease dementia. Keywords: Parkinson's disease dementia ; MPTP ; Species differences ; Motor function ; Anxiety level ; Learning ; Recognition ; Animal model Conference: Neuroinformatics 2010 , Kobe, Japan, 30 Aug - 1 Sep, 2010. Presentation Type: Poster Presentation Topic: Clinical neuroscience Citation: Chun Ho S and Jui Ho Y (2010). MPTP-induced Animal Model of Parkinson's Disease Dementia: There are Species Differences. Front. Neurosci. Conference Abstract: Neuroinformatics 2010 . doi: 10.3389/conf.fnins.2010.13.00094 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 14 Jun 2010; Published Online: 14 Jun 2010. * Correspondence: Shih Chun Ho, Chung Shan Medical University, School of Psychology, Taichung, Taiwan, gorgeous-1023@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Shih Chun Ho Ying Jui Ho Google Shih Chun Ho Ying Jui Ho Google Scholar Shih Chun Ho Ying Jui Ho PubMed Shih Chun Ho Ying Jui Ho Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Involvement of NMDA receptors in both MPTP-induced neuroinflammation and deficits in episodic-like memory in Wistar rats

Hyper-activation of glutamatergic activity and deficits in episodic memory has been observed in Parkinson's disease (PD). This study was intended to clarify the effects of d-cycloserine (DCS), a partial agonist of N-methyl-d-aspartate (NMDA) receptors, on neuroinflammation and deficits in episodic-like memory in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Male Wistar rats were stereotaxically administered with MPTP into the substantia nigra pars compacta. Starting 1 day after the lesion, animals were treated daily with DCS (0, 5, or 10mg/kg/day; i.p.). Thirteen days after the MPTP lesion, the rats received the episodic-like memory test. Sham-operated rats exhibited episodic-like memory, recognizing objects’ location and objects’ temporal order. MPTP-lesioned rats exhibited deterioration in spatial memory and failed to recognize the temporal order of objects. Further, MPTP lesions resulted in dopaminergic degeneration and microglial activation in the brain, as well as cell loss in the hippocampal CA1 area. DCS treatment (10mg/kg/day) reversed the above neurodegeneration, neuroinflammation, and behavioral deficits. Taken together, these results suggest that NMDA receptors may be involved in cognitive deficits in PD and that the application of DCS in the treatment for dementia in PD is warranted.

MPTP lesion causes neuroinflammation and deficits in object recognition in Wistar rats.

Animal models of Parkinson's disease with dementia would greatly facilitate research into the underlying causes of this disorder. Here, we showed that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, cell loss in the hippocampal CA1 area, as well as microglial activation and increase of interleukin-2 levels in several brain regions. In addition, increase of anxiety-like behavior and impairment of object recognition were observed in the MPTP-lesioned rats. These findings suggest that neuroinflammation may contribute to MPTP-induced neurodegeneration and behavioral deficits, which is suggested as an animal model of Parkinson's disease dementia.

Beneficial effects of pioglitazone on cognitive impairment in MPTP model of Parkinson's disease

The present study was carried out to elucidate the beneficial effect of pioglitazone in cognitive impairment induced by bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in substantia nigra pars compacta (SNc) in rats, a model of Parkinson's disease. MPTP-lesioned rats showed poor cognitive performance in both passive avoidance task and cued version of the Morris water maze test. This deficit in learning and memory was found to be associated with oxidative stress. Chronic administration of pioglitazone (10 and 30 mg/kg, p.o., starting 5 days prior to MPTP administration and then for next 30 days) in MPTP-lesioned rats improved cognitive performance in passive avoidance task and cued version of the Morris water maze test. Furthermore, pioglitazone treatment also reduced oxidative stress (as evident by reduced malondialdehyde and increased glutathione levels). These results demonstrate the beneficial effects of pioglitazone on cognitive impairment in MPTP induced Parkinson's disease in rats.

Melatonin attenuates tyrosine hydroxylase loss and hypolocomotion in MPTP-lesioned rats

Parkinson's disease is a chronic neurological disease characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. Melatonin is a powerful antioxidant agent secreted by the pineal gland which has numerous physiological functions and seems to exert an important neuroprotective effect. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model has been used to understand the pathophysiology of the disease because of its capacity to mimic biochemical and histological features observed in Parkinson's disease. This study investigated the effect of pretreatment with melatonin (50 mg/kg) on MPTP-lesioned animals 24 h and 7 days after neurotoxin infusion using the open-field test, two-way avoidance task and immunohistochemistry. Twenty-four hours after lesioning, the MPTP + vehicle group exhibited hypolocomotion and significant loss of tyrosine hydroxylase-immunoreactive cells, whereas no differences in these parameters were observed in lesioned animals receiving melatonin. Seven days after surgery, the MPTP-lesioned rats did not show hypolocomotion compared to control animals, while there was a significant dopaminergic neuronal loss. In the two-way avoidance task, MPTP-treated animals presented a cognitive deficit compared to the control groups and melatonin administration did not repair this defect. The present results suggest that melatonin reduces neuronal loss in the MPTP animal model of Parkinson's disease.

Intra-nigral MPTP lesion in rats: Behavioral and autoradiography studies

The present study investigated the motor response and possible changes in binding to D 1 and D 2 receptors after intra-nigral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion on rats. The results indicated that MPTP-lesioned rats exhibited a significant reduction in locomotion and rearing frequencies observed in an open field 24 h after surgery. However, at 7 and 14 days after surgery the MPTP-lesioned rats showed a significant increase in locomotion in comparison to the control groups, as well as a decrease in immobility time. In addition, 21 days after surgery the behavioral measurements were unaltered by these procedures. Moreover, latency in initiating movement and catalepsy were unchanged by this neurotoxin on the same days of observation. An autoradiography approach indicated that there was a reduction in [ 3H]SCH 23390 binding in substantia nigra pars compacta (SNpc), substantia nigra pars reticulata (SNpr) and ventrolateral striatum in MPTP-treated rats 21 days after the surgery. [ 3H]raclopride binding remained unaltered by the MPTP treatment. These results suggest that compensatory plastic changes occur in D 1 dopamine receptors after partial lesion of nigral dopaminergic neurons. These alterations might be related to the occurrence and recovery of motor impairment observed in MPTP-lesioned rats.

Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: Histological, neurochemical, motor and memory alterations

This study compares histological, neurochemical, behavioral, motor and cognitive alterations as well as mortality of two models of Parkinson's disease in which 100 μg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 μg 6-hydroxydopamine (6-OHDA) was bilaterally infused into the central region of the substantia nigra, compact part, of adult male Wistar rats. Both neurotoxins caused a significant loss of nigral tyrosine hydroxylase-immunostained cells and striatal dopamine depletion, but 6-OHDA caused more widespread and intense cell loss, more intense body weight loss and more mortality than MPTP. Both 6-OHDA- and MPTP-lesioned rats presented similar deficits in performing a working memory and a cued version of the Morris water maze task and few exploratory/motor alterations in the open field and catalepsy tests. However, rats presented a significant and transitory increase in locomotor activity after the MPTP lesion and a hypolocomotor behavior tended to be present after the 6-OHDA lesion. The picture of mild motor effects and robust impairment of habit learning and spatial working memory observed in MPTP-lesioned rats models the early phase of Parkinson's disease.

Behavioural and neurochemical effects of phosphatidylserine in MPTP lesion of the substantia nigra of rats

The present study investigated the effects of intranigral MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) infusion on rats treated with phosphatidylserine and evaluated in two memory tasks and on striatal dopamine levels. The results indicated that MPTP produced a significant decrease in the avoidance number in comparison to sham-operated and non-operated rats submitted to a two-way avoidance task. MPTP-lesioned rats exhibited an increase in the latencies to find the platform in cued version of the water maze in comparison to sham-operated and non-operated animals. The tested toxin reduced striatal dopamine levels in comparison to sham-operated and non-operated groups. A final surprising result was that phosphatidylserine was unable to reverse the cognitive deficits produced by MPTP or the reduction of striatal dopamine levels. In conclusion, the data suggest that MPTP is a good model to study the early impairment associated with Parkinson's disease and phosphatidylserine did not improve the memory impairment induced by MPTP.

L-Dopa restores striatal dopamine level but fails to reverse MPTP-induced memory deficits in rats.

The objective of the present investigation was to test the effects of benserazide/L-dopa treatment in a model of learning and memory deficits associated with early Parkinson's disease. Intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a lesion in the substantia nigra, compact part and a specific loss of dopamine (DA) and its metabolites in the striatum of rats and a memory impairment in the two-way active avoidance task. The administration of benserazide/L-dopa (50 and 200 mg/kg) to the MPTP-lesioned rats restored the striatal level of DA, but did not reverse the MPTP-induced learning and memory impairment. As this treatment caused a large increase of DA levels in extrastriatal brain regions of the MPTP-lesioned animals, this study suggests that benserazide/L-dopa therapy was not effective in improving the observed learning impairment because this treatment appears to tilt the balance between DA levels in the striatum and in the extrastriatal regions, such as frontal cortex and limbic structures, resulting in a cognitive deficit.