Neuropathology of the Basal Ganglia in SNCA Transgenic Rat Model of Parkinson's Disease: Involvement of Parvalbuminergic Interneurons and Glial-Derived Neurotropic Factor.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein, encoded by the SNCA gene. The main neuropathological hallmark of PD is the degeneration of dopaminergic neurons leading to striatal dopamine depletion. Trophic support by a neurotrophin called glial-derived neurotrophic factor (GDNF) is also lacking in PD. We performed immunohistochemical studies to investigate neuropathological changes in the basal ganglia of a rat transgenic model of PD overexpressing alfa-synuclein. We observed that neuronal loss also occurs in the dorsolateral part of the striatum in the advanced stages of the disease. Moreover, along with the degeneration of the medium spiny projection neurons, we found a dramatic loss of parvalbumin interneurons. A marked decrease in GDNF, which is produced by parvalbumin interneurons, was observed in the striatum and in the substantia nigra of these animals. This confirmed the involvement of the striatum in the pathophysiology of PD and the importance of GDNF in maintaining the health of the substantia nigra.

Emerging Role of NLRP3 Inflammasome/Pyroptosis in Huntington's Disease.

Huntington's disease (HD) is a neurodegenerative disease characterized by several symptoms encompassing movement, cognition, and behavior. The mutation of the IT15 gene encoding for the huntingtin protein is the cause of HD. Mutant huntingtin interacts with and impairs the function of several transcription factors involved in neuronal survival. Although many mechanisms determining neuronal death have been described over the years, the significant role of inflammation has gained momentum in the last decade. Drugs targeting the elements that orchestrate inflammation have been considered powerful tools to treat HD. In this review, we will describe the data supporting inflammasome and NLRP3 as a target of therapeutics to fight HD, deepening the possible mechanisms of action underlying these effects.

Early balance training with a computerized stabilometric platform in persons with mild hemiparesis in subacute stroke phase: A randomized controlled pilot study.

BACKGROUND: Along with conventional therapy, novel tools are being developed in balance training for the rehabilitation of persons with stroke sequelae. The efficacy of Computerized Balance Training thus far been the object of studies only in persons with chronic stroke. OBJECTIVE: To investigate the effects of an early Computerized Balance Training on balance, walking endurance and independence in activities of daily living, in persons with mild hemiparesis in subacute phase. METHODS: Thirty-two persons with a recent hemiparesis (within 4 weeks from stroke onset), able to maintain a standing position for at least 30 seconds, were randomly assigned to an experimental or control group. The control group (CG) were administered conventional physiotherapy of 40 minutes twice a day, 5 times a week for 4 weeks, while the experimental group (EG) underwent conventional physiotherapy 40 minutes once a day and Computerized Balance Training once a day, 5 times a week for 4 weeks. Outcomes were evaluated by means of Berg Balance Scale (BBS), Tinetti Balance Scale (TBS), Two Minutes Walk Test (2MWT), Barthel Index (BI) and stabilometric tests. RESULTS: Twelve participants for each group completed the training. Each group experienced 8 dropouts. The mean age (years) was 58.1±20.4 for EG and 59.7±14,7 for CG; the days from stroke were respectively 27.9±15.5 and 20±11.7. The difference between the two groups was statistically significant in experimental group for BBS (p = 0.003), for TBS (p = 0.028), for Sensory Integration and Balance tests performed with closed eyes on steady (p = 0.009) or instable surface (p = 0.023). and for 2MWT (p = 0.008). CONCLUSIONS: Computerized Balance Training is an effective therapeutic tool for balance and gait endurance improvement in persons with stroke in subacute phase.

Dystonia: Sparse Synapses for D2 Receptors in Striatum of a DYT1 Knock-out Mouse Model.

Dystonia pathophysiology has been partly linked to downregulation and dysfunction ofdopamine D2 receptors in striatum. We aimed to investigate the possible morpho-structuralcorrelates of D2 receptor downregulation in the striatum of a DYT1 Tor1a mouse model. Adultcontrol Tor1a+/+ and mutant Tor1a+/- mice were used. The brains were perfused and free-floatingsections of basal ganglia were incubated with polyclonal anti-D2 antibody, followed by secondaryimmune-fluorescent antibody. Confocal microscopy was used to detect immune-fluorescent signals.The same primary antibody was used to evaluate D2 receptor expression by western blot. The D2receptor immune-fluorescence appeared circumscribed in small disks (0.3-0.5 µm diameter), likelyrepresenting D2 synapse aggregates, densely distributed in the striatum of Tor1a+/+ mice. In theTor1a+/- mice the D2 aggregates were significantly smaller (µm2 2.4 ± SE 0.16, compared to µm2 6.73± SE 3.41 in Tor1a+/+) and sparse, with ~30% less number per microscopic field, value correspondentto the amount of reduced D2 expression in western blotting analysis. In DYT1 mutant mice thesparse and small D2 synapses in the striatum may be insufficient to "gate" the amount ofpresynaptic dopamine release diffusing in peri-synaptic space, and this consequently may result ina timing and spatially larger nonselective sphere of influence of dopamine action.

Early body weight-supported overground walking training in patients with stroke in subacute phase compared to conventional physiotherapy: a randomized controlled pilot study.

Among the new rehabilitation strategies aimed at improving independent walking after stroke, the body weight-support training allows an early and controlled ambulatory training. To date, most available studies are based on treadmill body weight-support (BWS) training and involve patients with chronic stroke sequelae. In contrast, the effects of a BWS training performed on the ground in patients with subacute hemiparesis (stroke within 4 weeks), with significant gait deficiencies, is unknown. The primary aim of this study was to evaluate the efficacy of a rehabilitative program that combines conventional approach with an early overground body weight-support training, in terms of recovery of independent walking focussing on patients with subacute stroke. The secondary aim was to evaluate the impact of body weight-support also on functional mobility, overall disability, and gait endurance. A total of 37 participants were enrolled and randomized to experimental group or control group for the baseline evaluations. In the experimental group, body weight-supported overground walking was added to conventional physiotherapy for 4 weeks. The outcome measurements used were: Functional Ambulation Classification (FAC), Rivermead Mobility Index, Barthel Index, and the 6-minute Walk Test. At the evaluation 1 week after the end of the intervention period, experimental group reached a statistically significant increase of independent walking as detected by FAC (experimental group: 3 vs. control group: 2, P < 0.01). No differences were observed by the other evaluation outcome measures. We conclude that BWS training may be more effective than conventional therapy alone in improving walking autonomy in persons with subacute stroke.

Bilateral upper limb rehabilitation with videogame-based feedback in corticobasal degeneration: a case reports study.

Corticobasal degeneration (CBD) is a neurodegenerative disorder characterized by a combination of cortical and basal ganglia signs. We reported two cases treated with a bilateral upper limb rehabilitation tool with videogame based feedback for 3 time per week for 8 weeks. Both patients showed an improvement of pinch and grasp forces and motor function. However, both of them reported an increased upper limb pain. Bilateral upper limb mechanical device with exergame feedback was effective also in the two patients suffering of CBD for limiting the effects of apraxia by performing intensive purposeful task training.

Correction: Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington's Disease.

[This corrects the article DOI: 10.1371/journal.pone.0064037.].

Persistent activation of microglia and NADPH oxidase [corrected] drive hippocampal dysfunction in experimental multiple sclerosis.

Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression.

Leap motion controlled videogame-based therapy for rehabilitation of elderly patients with subacute stroke: a feasibility pilot study.

BACKGROUND: The leap motion controller (LMC) is a new optoelectronic system for capturing motion of both hands and controlling a virtual environment. Differently from previous devices, it optoelectronically tracks the fine movements of fingers neither using glows nor markers. OBJECTIVE: This pilot study explored the feasibility of adapting the LMC, developed for videogames, to neurorehabilitation of elderly with subacute stroke. METHODS: Four elderly patients (71.50 ± 4.51 years old) affected by stroke in subacute phase were enrolled and tested in a cross-over pilot trial in which six sessions of 30 minutes of LMC videogame-based therapy were added on conventional therapy. Measurements involved participation to the sessions, evaluated by means of the Pittsburgh Rehabilitation Participation Scale, hand ability and grasp force evaluated respectively by means of the Abilhand Scale and by means of the dynamometer. RESULTS: Neither adverse effects nor spasticity increments were observed during LMC training. Participation to the sessions was excellent in three patients and very good in one patient during the LMC trial. In this period, patients showed a significantly higher improvement in hand abilities (P = 0.028) and grasp force (P = 0.006). CONCLUSIONS: This feasibility pilot study was the first one using leap motion controller for conducting a videogame-based therapy. This study provided a proof of concept that LMC can be a suitable tool even for elderly patients with subacute stroke. LMC training was in fact performed with a high level of active participation, without adverse effects, and contributed to increase the recovery of hand abilities.

Systemic delivery of recombinant brain derived neurotrophic factor (BDNF) in the R6/2 mouse model of Huntington's disease.

Loss of huntingtin-mediated BDNF gene transcription has been shown to occur in HD and thus contribute to the degeneration of the striatum. Several studies have indicated that an increase in BDNF levels is associated with neuroprotection and amelioration of neurological signs in animal models of HD. In a recent study, an increase in BDNF mRNA and protein levels was recorded in mice administered recombinant BDNF peripherally. Chronic, indwelling osmotic mini-pumps containing either recombinant BDNF or saline were surgically placed in R6/2 or wild-type mice from 4 weeks of age until euthanasia. Neurological evaluation (paw clasping, rotarod performance, locomotor activity in an open field) was performed. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that BDNF- treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as brain volume, striatal atrophy, size and morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. BDNF was effective in increasing significantly the levels of activated CREB and of BDNF the striatal spiny neurons. Moreover, systemically administered BDNF increased the synthesis of BDNF as demonstrated by RT-PCR, and this might account for the beneficial effects observed in this model.

Effects of central and peripheral inflammation on hippocampal synaptic plasticity.

The central nervous system (CNS) and the immune system are known to be engaged in an intense bidirectional crosstalk. In particular, the immune system has the potential to influence the induction of brain plastic phenomena and neuronal networks functioning. During direct CNS inflammation, as well as during systemic, peripheral, inflammation, the modulation exerted by neuroinflammatory mediators on synaptic plasticity might negatively influence brain neuronal networks functioning. The aim of the present study was to investigate, by using electrophysiological techniques, the ability of hippocampal excitatory synapses to undergo synaptic plasticity during the initial clinical phase of an experimental model of CNS (experimental autoimmune encephalomyelitis, EAE) as well as following a systemic inflammatory trigger. Moreover, we compared the morphologic, synaptic and molecular consequences of central neuroinflammation with those accompanying peripheral inflammation. Hippocampal long-term potentiation (LTP) has been studied by extracellular field potential recordings in the CA1 region. Immunohistochemistry was performed to investigate microglia activation. Western blot and ELISA assays have been performed to assess changes in the subunit composition of the synaptic glutamate NMDA receptor and the concentration of pro-inflammatory cytokines in the hippocampus. Significant microglial activation together with an impairment of CA1 LTP was present in the hippocampus of mice with central as well as peripheral inflammation. Interestingly, exclusively during EAE but not during systemic inflammation, the impairment of hippocampal LTP was paralleled by a selective reduction of the NMDA receptor NR2B subunit levels and a selective increase of interleukin-1ß (IL1ß) levels. Both central and peripheral inflammation-triggered mechanisms can activate CNS microglia and influence the function of CNS synapses. During direct CNS inflammation these events are accompanied by detectable changes in synaptic glutamate receptors subunit composition and in the levels of the pro-inflammatory cytokine IL1ß.

Ischemic-LTP in striatal spiny neurons of both direct and indirect pathway requires the activation of D1-like receptors and NO/soluble guanylate cyclase/cGMP transmission.

Striatal medium-sized spiny neurons (MSNs) are highly vulnerable to ischemia. A brief ischemic insult, produced by oxygen and glucose deprivation (OGD), can induce ischemic long-term potentiation (i-LTP) of corticostriatal excitatory postsynaptic response. Since nitric oxide (NO) is involved in the pathophysiology of brain ischemia and the dopamine D1/D5-receptors (D1-like-R) are expressed in striatal NOS-positive interneurons, we hypothesized a relation between NOS-positive interneurons and striatal i-LTP, involving D1R activation and NO production. We investigated the mechanisms involved in i-LTP induced by OGD in corticostriatal slices and found that the D1-like-R antagonist SCH-23390 prevented i-LTP in all recorded MSNs. Immunofluorescence analysis confirmed the induction of i-LTP in both substance P-positive, (putative D1R-expressing) and adenosine A2A-receptor-positive (putative D2R-expressing) MSNs. Furthermore, i-LTP was dependent on a NOS/cGMP pathway since pharmacological blockade of NOS, guanylate-cyclase, or PKG prevented i-LTP. However, these compounds failed to prevent i-LTP in the presence of a NO donor or cGMP analog, respectively. Interestingly, the D1-like-R antagonism failed to prevent i-LTP when intracellular cGMP was pharmacologically increased. We propose that NO, produced by striatal NOS-positive interneurons via the stimulation of D1-like-R located on these cells, is critical for i-LTP induction in the entire population of MSNs involving a cGMP-dependent pathway.

A2A adenosine receptor antagonism enhances synaptic and motor effects of cocaine via CB1 cannabinoid receptor activation.

BACKGROUND: Cocaine increases the level of endogenous dopamine (DA) in the striatum by blocking the DA transporter. Endogenous DA modulates glutamatergic inputs to striatal neurons and this modulation influences motor activity. Since D2 DA and A2A-adenosine receptors (A2A-Rs) have antagonistic effects on striatal neurons, drugs targeting adenosine receptors such as caffeine-like compounds, could enhance psychomotor stimulant effects of cocaine. In this study, we analyzed the electrophysiological effects of cocaine and A2A-Rs antagonists in striatal slices and the motor effects produced by this pharmacological modulation in rodents. PRINCIPAL FINDINGS: Concomitant administration of cocaine and A2A-Rs antagonists reduced glutamatergic synaptic transmission in striatal spiny neurons while these drugs failed to produce this effect when given in isolation. This inhibitory effect was dependent on the activation of D2-like receptors and the release of endocannabinoids since it was prevented by L-sulpiride and reduced by a CB1 receptor antagonist. Combined application of cocaine and A2A-R antagonists also reduced the firing frequency of striatal cholinergic interneurons suggesting that changes in cholinergic tone might contribute to this synaptic modulation. Finally, A2A-Rs antagonists, in the presence of a sub-threshold dose of cocaine, enhanced locomotion and, in line with the electrophysiological experiments, this enhanced activity required activation of D2-like and CB1 receptors. CONCLUSIONS: The present study provides a possible synaptic mechanism explaining how caffeine-like compounds could enhance psychomotor stimulant effects of cocaine.

The distinct role of medium spiny neurons and cholinergic interneurons in the D2/A2A receptor interaction in the striatum: implications for Parkinson's disease.

A(2A) adenosine receptor antagonists are currently under investigation as potential therapeutic agents for Parkinson's disease (PD). However, the molecular mechanisms underlying this therapeutic effect is still unclear. A functional antagonism exists between A(2A) adenosine and D(2) dopamine (DA) receptors that are coexpressed in striatal medium spiny neurons (MSNs) of the indirect pathway. Since this interaction could also occur in other neuronal subtypes, we have analyzed the pharmacological modulation of this relationship in murine MSNs of the direct and indirect pathways as well in striatal cholinergic interneurons. Under physiological conditions, endogenous cannabinoids (eCBs) play a major role in the inhibitory effect on striatal glutamatergic transmission exerted by the concomitant activation of D(2) DA receptors and blockade of A(2A) receptors in both D(2)- and D(1)-expressing striatal MSNs. In experimental models of PD, the inhibition of striatal glutamatergic activity exerted by D(2) receptor activation did not require the concomitant inhibition of A(2A) receptors, while it was still dependent on the activation of CB(1) receptors in both D(2)- and D(1)-expressing MSNs. Interestingly, the antagonism of M1 muscarinic receptors blocked the effects of D(2)/A(2A) receptor modulation on MSNs. Moreover, in cholinergic interneurons we found coexpression of D(2) and A(2A) receptors and a reduction of the firing frequency exerted by the same pharmacological agents that reduced excitatory transmission in MSNs. This evidence supports the hypothesis that striatal cholinergic interneurons, projecting to virtually all MSN subtypes, are involved in the D(2)/A(2A) and endocannabinoid-mediated effects observed on both subpopulations of MSNs in physiological conditions and in experimental PD.

Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

BACKGROUND: Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse. METHODOLOGY/PRINCIPAL FINDINGS: R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated. CONCLUSIONS/SIGNIFICANCE: Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More significantly, our studies point directly to an accessible new therapeutic approach to slow Huntington's disease progression, namely, PDE10A inhibition. There is considerable activity throughout the pharmaceutical industry to develop PDE10A inhibitors for the treatment of basal ganglia disorders. The present results strongly support the investigation of PDE10A inhibitors as a much needed new treatment approach to Huntington's disease.

A case of PANDAS treated with tetrabenazine and tonsillectomy.

PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) is a rare clinical syndrome characterized by the presence of tics, Tourette syndrome, obsessive-compulsive disorder, or chorea in the context of an immediately precedent streptococcal infection. In this report, we describe the case of an 11-year-old boy who developed PANDAS with severe choreic movements. The criteria for PANDAS diagnosis were met. Moreover, serum antibrain antibodies were present. The patient was initially treated with tetrabenazine 12.5 mg twice daily with remission of the neurological symptoms. Subsequently, the patient underwent tonsillectomy and has been asymptomatic since, with antistreptolysin O titer levels in range.

Quantification of the probability of reaching mobility independence at discharge from a rehabilitation hospital in nonwalking early ischemic stroke patients: a multivariate study.

BACKGROUND: This study was designed to quantify the probability of recovery of mobility in admission nonwalking stroke survivors. METHODS: We evaluated 437 of 500 consecutive patients admitted for sequelae of first ischemic stroke within the first month. We performed several logistic regressions using mobility status at discharge (independence in stair climbing; walking outside and inside, without aid or supervision; walking with cane or other aid, or need for wheelchair) as dependent variable, and several independent variables, including stratification of patients according to their Barthel Index (BI) score into 6 classes (< or =10; 11-20; 21-30; 31-40; 41-50; 51-60). RESULTS: At discharge, 4.58% of patients were independent in stair climbing, 8.70% were able to walk outside, 14.41% to walk inside, and 27.46% to walk with cane or other aid, while 44.85% remained in wheelchair. Very low BI scores at admission were associated with a high risk of need for wheelchair, whereas patients with BI score 51-60 showed a high probability to reach independence in stair climbing (OR = 5.60). Age, severity of neurological impairment, global aphasia, unilateral spatial neglect, male gender and vocational status also played a prognostic role. CONCLUSIONS: The probability of potential mobility recovery can be quantified at admission with better accuracy for independence in stair climbing and walking outside without any aid (percentages correctly predicted 95.4 and 91.8%, respectively). Stratification of BI score may be useful to better quantify the risk for each patient.

Beneficial effects of rolipram in the R6/2 mouse model of Huntington's disease.

We have previously showed that rolipram, a phosphodiesterase type IV inhibitor, displays a neuroprotective effect in a rat quinolinic acid model of HD [DeMarch Z., Giampa C., Patassini S., Martorana A., Bernardi G. and Fusco F.R., (2007) Beneficial effects of rolipram in a quinolinic acid model of striatal excitotoxicity. Neurobiol. Dis. 25:266-273.]. In this study, we sought to determine if rolipram exerts a neuroprotective effect in R6/2 mutant mice, which recapitulates, in many aspects, human HD [Mangiarini L., Sathasivam K., Seller M., Cozens B., Harper A., Hetherington C., Lawton M., Trottier Y., Lehrach H., Davies S.W. and Bates G.P. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell. 87:493-506]. Transgenic mice were treated with rolipram 1.5 mg/kg daily starting from 4 weeks of age. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that rolipram-treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as brain volume, striatal atrophy, size and morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. Rolipram was effective in increasing significantly the levels of activated CREB and of BDNF the striatal spiny neurons, which might account for the beneficial effects observed in this model. Our findings show that rolipram could be considered as a valid therapeutic approach for HD.

Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease.

Huntington's disease (HD) is a progressive neurodegenerative disorder, characterised by severe degeneration of basal ganglia, motor abnormalities, impaired cognitive function and emotional disturbances. Many of the distinct neuropathological features of HD are reproduced in rats by intrastriatal injections of the excitotoxin quinolinic acid (QA), and QA-induced excitotoxicity is partially prevented by administration of the A(2A) receptor antagonist prior to the QA injection. In this study, we assessed the neuroprotective effects of the adenosine A(2A) receptor antagonist SCH 58261 on the progressive behavioural alterations reported in the QA rat model of Huntington's disease. Male rats received i.p. SCH 58261 (0.01mg/kg) or vehicle 20min before a bilateral injection of quinolinic acid (QA, 300nmol/1mul) or its vehicle in the dorsal striatum. Motor activity and anxiety levels were analyzed in an open-field arena and in an elevated plus-maze at 2 weeks, 2 months and 6 months post-lesion. In QA-lesioned rats SCH 58261 prevented alterations of wall rearing behaviour starting from 2 weeks post-lesion while emotional changes (reduced anxiety) were back to control levels by 6 months post-lesion. These findings extend to the behavioural parameters the protective effects of SCH 58261 in the QA model of Huntington's disease.