Reduction In Spontaneous Motor Activity Research Articles

CNS DEPRESSANT ACTIVITY OF KASHAYA OF ASOKA – SARACA ASOCA ROXB. DE (WILDE.)

Ayurveda explains chikitsa (treatment – mode to attain health) as a conglomeration of chatushpada’s (four limbs). Pharmacological categorization of drugs can be explored for the first time from the Charaka Samhita, Shadvirechana Shatasriteeya Adhyaya. Asoka - Saraca asoca [Roxb] de Wilde has been included in the Vedanasthapana mahakashaya (group of drugs which alleviates a specific sensation) mentioned by Acharya Charaka, which is explained as streenam uchrokanashanaya by the Nighantukaara’s. The etymology of soka is chittavikalatha, which is a ‘lead’ to the action of a drug on “manasika bhava’s”. In clinical experience, apart from the pain, associated symptoms like nausea, vomiting, delirium, insomnia, emotional instability, nervousness, irritability, anger, and fear are also relieved by its usage. Till now, the pharmacological action of Asoka on “manasika bhava’s” remains unexplored. Hence, a preliminary experimental study has been undertaken on the reverse pharmacological aspect to assess the action of this drug on CNS. The depressant action of drugs on CNS is mediated through both neural and hormonal mechanisms. The immediate reduction in spontaneous motor activity was achieved through the neural mechanism, and the prolonged effect was achieved through the hormonal action. The drug possesses bitter principles. The functional bitter taste is expressed in brain cells by bitter taste receptors T2R’s. T2R-4, T2R-107, and T2R-38 transcripts are found in the brain stem, cerebral cortex and cerebellum. The drug is a potent source of phytoestrogen, which has oestrogen-mimicking action. The drug significantly reduces spontaneous motor activity in the CNS depressant activity study on all assessment days, with a p-value.

Tramadol and Codeine Stacking/Boosting Dose Exposure Induced Neurotoxic Behaviors, Oxidative Stress, Mitochondrial Dysfunction, and Neurotoxic Genes in Adolescent Mice

In spite of the increasing epidemic of pharmaceutical opioids (codeine and tramadol) misuse and abuse among the adolescents, little is known about the neurotoxic consequences of the widespread practice of tramadol and codeine abuse involving increasing multiple doses across days, referred to as stacking and boosting. Hence, in this study, we replicated stacking and boosting doses of tramadol, codeine alone, or in combination on spontaneous motor activity and cognitive function in adolescent mice and adduced a plausible mechanism of possible neurotoxicity. Ninety-six adolescent mice were randomly distributed into 4 groups (n = 24 per group) and treated thrice daily for 9days with vehicle, tramadol (20, 40, or 80mg/kg), codeine (40, 80, or 160mg/kg), or their combinations. Exposure of mice to tramadol induced hyperactivity and stereotypic behavior while codeine exposure caused hypoactivity and nootropic effect but tramadol-codeine cocktail led to marked reduction in spontaneous motor activity and cognitive function. In addition, tramadol, codeine, and their cocktail caused marked induction of nitroso-oxidative stress and inhibition of mitochondrial complex I activity in the prefrontal cortex (PFC) and midbrain (MB). Real-time PCR expression profiling of genes encoding neurotoxicity (RT) showed that tramadol exposure upregulate 57 and downregulate 16 neurotoxic genes, codeine upregulate 45 and downregulate 25 neurotoxic genes while tramadol-codeine cocktail upregulate 52 and downregulate 20 neurotoxic genes in the PFC. Findings from this study demonstrate that the exposure of adolescents mice to multiple and increasing doses of tramadol, codeine, or their cocktail lead to spontaneous motor coordination deficits indicative of neurotoxicity through induction of oxidative stress, inhibition of mitochondrial complex I activity and upregulation of neurotoxicity encoding genes in mice.

Differential behavioral and glial responses induced by dopaminergic mechanisms in the iNOS knockout mice

The interaction between distinctive nitric oxide synthase (NOS) isoforms and the dopamine system provides new avenues to the development of pharmacological tools for the pathophysiological conditions of the dopaminergic system. Our aim was to investigate the influences of dopamine-induced effects in inducible NOS knockout (iNOS KO) mice. In order to characterize iNOS KO mice phenotype, the animals were submitted to the basal analyses of motor, sensorimotor and sensorial abilities. Pharmacological challenging of the dopaminergic system included the investigation of amphetamine-induced prepulse inhibition (PPI) disruption, haloperidol-induced catalepsy, reserpine-induced oral involuntary movements and hyperlocomotion induced by amphetamine in reserpine treated mice. The iNOS KO mice showed significant reduction of spontaneous motor activity, but there was no significant difference in sensorimotor or sensorial responses of iNOS KO mice compared to wild type (WT). Regarding the dopaminergic system, iNOS KO mice showed a significant increase of haloperidol-induced catalepsy. This effect was confirmed through an iNOS pharmacological inhibitor (1400 W) in WT mice. In addition, iNOS KO reserpine treated mice showed reduced oral involuntary movements and amphetamine-induced hyperlocomotion. Knowing that iNOS is mainly expressed in glial cells we analyzed the immunoreactivity (ir) for GFAP (astrocyte marker) and IBA-1 (microglial marker) in the striatum, an area enrolled in motor planning among other functions. iNOS KO presented reduced GFAP-ir and IBA-1-ir compared with WT. Reserpine treatment increased GFAP-ir in both WT and iNOS KO. However, these effects were slighter in iNOS KO. Activated state of microglia was increased by reserpine only in WT mice. Our results further demonstrated that the absence of iNOS interfered with dopamine-mediated behavioral and molecular responses. These results increase the understanding of the dopamine and NO system interaction, which is useful for the management of the dopamine-related pathologies.

Enhancement of Pentobarbital-induced Sleep by the Vaporized Essential Oil of Citrus keraji var. kabuchii and its Characteristic Component, γ-Terpinene

Kabuchii (Citrus keraji var. kabuchii hort. ex Tanaka, Rutaceae) is a peculiar Okinawan citrus fruit. Local farmers cultivating various Citrus fruits say that the fragrance of Kabuchii is the most relaxing, but, there are few reports on the biological effects of the essential oil of Kabuchii and its chemical components [1]. In this study, the sedative effects of inhalation of the vaporized Kabuchii essential oil in open field, Rotarod, and pentobarbital sleep tests are compared with diazepam, as a positive control. In the open field test, both Kabuchii essential oil and diazepam decreased the spontaneous motor activity dose-dependently. The reduction in spontaneous motor activity in the 0.3 mg/cage (ca. 0.0278 mg/L) Kabuchii essential oil group was greater than that in the 1 mg/kg diazepam group. In the Rotarod test, Kabuchii did not affect the motor performance, even at the highest dosage tested (3 mg/cage), whereas diazepam decreased it dose- dependently. The effects of the major or characteristic components of Kabuchii, d-limonene, y-terpinene, thymol, and p-cymene, were also evaluated in the- open field and Rotarod tests. y-Terpinene and thymol significantly decreased spontaneous motor activity at a dosage of 0.3 mg/cage, without affecting motor performance. Thus, y-terpinene was estimated to be the main active component. Reduction in spontaneous motor activity by y-terpinene in the open field test was not observed in intranasal zinc sulfate irrigation-induced anosmic mice. In the pentobarbital sleep test, both Kabuchii essential oil and diazepam potentiated pentobarbital-induced loss of the righting reflex (LRR). The LRR duration prolonging effects of both treatments were inhibited by pretreatment with flumazenil, a benzodiazepine receptor antagonist. The LRR latency reducing effect of Kabuchii was not affected by flumazenil, while that of diazepam was suppressed by it. y-Terpinene showed similar potentiating effects on pentobarbital-induced sleep. Thus, vaporized Kabuchii essential oil and its active component, y-terpinene, have sedative effects comparable with diazepam without inducing motor incoordination, which is a well-known side effect of. diazepam.

Tamizaje fitoquímico y evaluación de la actividad sobre el sistema nervioso central del extracto etanólico de Eugenia clarensis Britton & P.Wilson

Context: Eugenia clarensis Britton & P. Wilson is an endangered plant endemic of central region of Cuba. Aims: To perform phytochemical profile of ethanolic leaf extract of E. clarensis and evaluate its central nervous system (CNS) activity. Methods: The dried powder of leaves of E. clarensis was exhaustively extracted with ethanol by maceration. This extract underwent preliminary phytochemical analysis and these results were corroborated by the thin layer chromatographic technique. CNS effects were investigated in NMRI mice at doses 200, 400 and 800 mg/kg using Irwin test, curiosity tests and traction. Results: Phytochemical screening suggested the presence of phenols, tannins, triterpenoids, sterols, flavonoids, coumarins, quinones, resins and reducing sugar. The oral administration of this extract, in Irwin test, produced slight reduction in spontaneous motor activity and muscle tone in mice at doses of 400 and 800 mg/kg, moreover, it exhibited diuretic activity. In addiction this extract at dose 800 mg/kg decreased number of times which mice introduced its head into holes in comparison with the negative control. In the traction test, the mice treated with the extract showed a non-significant failure in traction at all doses tested. Conclusions: These findings indicate that the extract in higher doses has exerts a weak sedative and non-effect about the motor coordination. The results obtained in the preliminary phytochemical testing thus suggest that the ethanolic leaf extract of E. clarensis contains some metabolites, which may be responsible of sedative action.

Neuropharmacological evaluation of Pentapetes phoenicea Linn. extracts

Background: The plant Pentapetes phoenicea was traditionally used to treat central nervous system disorders. The present study was conducted to evaluate the neuropharmacology of the plant using various methods involving rats and mice. Objective: The study probes the neuropharmacological activities of P. phoenicea in rats and mice. Materials and Methods: The effect of the extracts on pentobarbitone-induced sleeping time, different models of seizures, spontaneous motor activity, exploratory behavior, and motor co-ordination were evaluated. Results: The extracts elicited significant prolongation of pentobarbitone-induced sleeping time, reduction in spontaneous motor activity, and exploratory behavior. The extracts prolonged the onset of seizures. Significant muscle relaxation was expressed in extract treated groups. Gamma-aminobutyric acid (GABA) levels were elevated in rats pretreated with P. phoenicea. Reversed-phase high-performance liquid chromatography was performed to rutin isolated from a methanolic extract of P. phoenicea. Conclusion: The results confirmed that P. phoenicea possesses significant anxiolytic potential with sedative action, and the mechanism underlying involves GABAnergic activity.

Effect of λ-Cyhalothrin on Redox Homeostasis and Neuropharmacological Activities in Wistar Rats

The present study was carried out to assess the behavioral, neurobiochemical changes following λ-cyhalothrin exposure and to evaluate the neuropharmacological activity in in Wistar rats using well defined animal models. Neurobehavioral assessment was carried as per modified Irwin test. To determine the oxidative profile of brain tissue, rats were randomly divided into two groups consisting of six rats each. Group I served as vehicle-treated control and Group II received λ-cyhalothrin at 7.8 mg/kg (per os) for a period of 7 days. The neuropharmacological studies were carried out in rats following administration of λ-cyhalothrin at a dose rate (per os) of either 1/5th or 1/10th LD50. Neurobehavioral assessment showed prominent autonomic sign(s) followed by depression following single administration of λ-cyhalothrin (1/10th LD50). Short-term exposure to λ-cyhalothrin-induced lipid peroxidation as evident by significant increase in malondialdehyde levels in the brain tissue. Marked alteration of antioxidant defense mechanism(s) in the brain tissue was observed by the reduced activity of superoxide dismutase and catalase. Further, the tissue glutathione (GSH) (reduced; GSH) content was also significantly (P < 0.05) depleted. λ-cyhalothrin exerted a significant reduction in spontaneous motor activity as well as forced motor activity in dose-dependent manner, thus demonstrated reduced activity of central nervous system. Interestingly, λ-cyhalothrin exerted nociceptive action, which was comparable to control group. Further, there was marked increase in the duration of strychnineinduced (2 mg/kg; i.p.) tonic-clonic convulsions in rats. Overall, short-term exposure to sub lethal dose of λ-cyhalothrin causes disturbances in brain redox homeostasis and alters neuropharmacological activity in Wistar rats.

Neuro-pharmacological effects of Crinum zeylanicum in mice.

The aim of present study was to evaluate some effects of Crinum zeylanicum (C. zeylanicum) on central nervous system. C. zeylanicum methanolic bulb extract (250-1000 mg/kg orally), 2 mg chlorpromazine and 4 mg diazepam /kg body weight intraperitoneally respectively were tested in mice using Irwin test, pentobarbitone-induced sleep test, spontaneous motor activity, apomorphine-induced stereotype behaviour, and rota-rod performance. The C. zeylanicum bulb extract significantly and dose-dependently decreased apomorphine-induced hyperactivity in mice (p<0.001). The Irwin test revealed dose-dependent central depressant effect of the extract, shortened (p<0.05-0.01) the onset of sleep and prolonged the duration of sleep. The extract produced significant (p<0.05-0.001) and dose- dependent reduction in spontaneous motor activity and apomorphine-induced stereotype behaviours in mice. The extract had no effect on performance of mice on rotarod. The results suggest that the extract may possess sedative principles with potential neuroleptic properties.

Potential of Pandanus odoratissimus as a CNS depressant in Swiss albino mice

In this study, several neuropharmacological effects of methanolic leaf extract of Pandanus odoratissimus (PO) (family; Pandanaceae) were studied in albino mice using various experimental models. The effect of PO on the CNS was studied by using different neuropharmacological paradigms including spontaneous motor activity, rota-rod performance and potentiation of Pentobarbital sodium sleeping time in albino mice. Preliminary phytochemical evaluation and acute toxicity studies were also carried out where LD50 &gt;2000 mg/kg was considered non-toxic through acute exposure in rats by the oral route. The methanolic leaf extract (50,100 and 200 mg/kg i. p.) produced a reduction in spontaneous motor activity, motor coordination and prolonged Pentobarbital sodium sleeping time. Preliminary qualitative chemical studies indicated the presence of steroids, saponins, terpinoids, glycosides, tannins, flavonoids and phenolics in the extract. These observations suggest that the leaf of Pandanus odoratissimus contains some active principles which possess potential CNS-depressant action

Antipsychotic property of aqueous and ethanolic extracts of Lonchocarpus cyanescens (Schumach and Thonn.) Benth. (Fabaceae) in rodents

Lonchocarpus cyanescens (LC) is a medicinal plant commonly used in combination with other recipes in the treatment of psychotic disorders in traditional medicine. This study was designed to examine whether the aqueous and ethanolic extracts of LC possess antipsychotic property in rats. The antipsychotic effects of the extracts were assessed using the amphetamine animal model of psychosis in rats. The effect of the extracts on spontaneous motor activity was also studied in the open field test in mice. The extrapyramidal side effect of catalepsy was tested based on the ability of the extracts to alter the duration of akinesia in mice placed on a vertical wrapped string. Aqueous and ethanolic extracts of LC (25-400 mg/kg, i.p.) significantly (p < 0.05) suppressed stereotyped behaviour induced by amphetamine (10.0 mg/kg, i.p.) in rats, which suggest antipsychotic activity. The extracts (25-400 mg/kg, i.p.) further produced a significant (p < 0.05) reduction in spontaneous motor activity of the animals in the open field test. However, in contrast to chlorpromazine, a typical antipsychotic, the extracts did not induce cataleptic behaviour in the animals. Preliminary phytochemical screening showed the presence of alkaloids, anthraquinones, cardiac glycosides, cyanogenetic glycosides, flavonoids, saponins, steroids and tannins in the leaves of LC. The presence of these secondary metabolites was confirmed by thin-layer chromatography. Taken together, these findings suggest that the extracts possess phytochemically active constituents with antipsychotic property. Thus, this investigation provides evidence that may justify the ethnomedicinal applications of Lonchocarpus cyanescens as the major constituent of the recipe used for the management of psychosis in Nigeria.

Some neuropharmacological effects of the methanolic root extract of Cissus quadrangularis in mice.

In this study, some neuropharmacological effects of methnolic root extractof Cissus quadrangularis Linn. (CQ) belongs to family Vitaceae werestudied in mice using various models. The CQ root extract significantlyinhibited acetic acid-induced writhings and increased tail flick withdrawalresponse in mice. The effects of CQ on CNS were studied by using,spontaneous motor activity, exploratory behaviour, rota-rod performanceand potentiation of pentobarbitone sleeping time in mice. Preliminaryphytochemical evaluation and acute toxicity values were also carried outand LD50 was found to be 1000 mg/kg by i p route. The extract (50,100and 200 mg/kg i. p.) produced reduction in spontaneous motor activity,exploratory behaviour and motor coordination and prolongedpentobarbitone sleeping time. Preliminary qualitative chemical studiesindicated the presence of triterpenoids, flovonols, sapononis, and alkaloidsin the extract. The results suggest that the methanolic root extract of CQcontains some active principles, which may be sedative in nature. (Afr. J.Biomed. Res. 9:69 – 75, May 2006) Keywords: Cissus quadrangularis; Sedation; Spontaneous motor activity, ExploratoryBehaviour, Motor coordination, Pentobarbital sleeping time

Some Neuropharmacological Effects of the Crude Venom Extract of &lt;i&gt;Conus musicus&lt;/i&gt; in Mice

This study reports some neuropharmacological effects of the crude venom extract of Conus musicus (family Conidae) in mice using various experimental models. The crude venom was found to significantly increase tail flick reaction time in mice. The effects of the venom on the central nervous system were studied by observing spontaneous motor activity, gross behaviour, rota-rod performance and potentiation of pentobarbitone sleeping time in mice. Preliminary acute toxicity evaluation was also carried out and the LD50 was found to be 460.23 &#956;g/kg following intraperitoneal administration. At a dose of 200 &#956;g/kg i.p., the extract produced a reduction in spontaneous motor activity, altered gross behavior and motor coordination and prolonged pentobarbitone-sleeping time. A liquid chromatography mass spectroscopic study has indicated the presence of &#969;-conotoxin in the crude venom extract. Keywords: Conus musicus, sedation, spontaneous motor activity, gross behavior, motor coordination East and Central African Journal of Pharmaceutical Sciences Vol. 10 (2) 2007: pp. 27-33

Some Neuropharamacological Effects of the Crude Extract of Conus parvatus in Mice

The present study was aimed to characterize the type of conotoxin present in Conus parvatus. (CP) belongs to family conidae, through neuro-pharmacological activities of the crude venom extract on some of the CNS animal experiment using mice as animal model. The effects of CP on CNS were studied, by using spontaneous motor activity, gross behavior, rota-rod performance, analgesic activity and potentiation of pentobarbitone sleeping time in mice. Preliminary evaluation of acute toxicity was also carried out; The LD50 value was found to be 425.20 mcg kg(-1) by i.p. route. The extract (200 mcg kg(-1) i.p.) was found to produce, reduction in spontaneous motor activity, potent analgesic activity, reduction in motor coordination and prolonged pentobarbitone-sleeping time. From the above all pharmacological activities, it may concluded that, the conotoxin present in CP is most likely to be a alpha-conotoxin and also it will be more suitable to continue the studies in the areas of analgesic and other CNS depressant therapeutic areas after isolation of the pure cono-peptide from CP.

Neuropharmacology of an Extract Derived from Centella asiatica

The hydroalcoholic extract of Centella asiataica L. leaves was subjected to pharmacological screening using various experimental models. The extract was found to show protective action against increase in current electroshock (ICES) and chemoconvulsions, which includes pentylenetetrazol-induced convulsions, pentylenetetrazol-kindled seizures, and strychnine-induced opisthotonus tonic convulsions. It also showed a reduction in formation of lipid peroxidation products, reduction in spontaneous motor activity, potentiation in diazepam withdrawal-induced hyperactivity, hypothermia, and potentiation of pentobarbitone sleeping time. An extract was administered orally to the animals in all the studies. The extract (200 mg/kg body weight) completely inhibited pentylenetetrazol-induced convulsions. In pentylenetetrazol-kindled seizures and strychnine-induced convulsions, the extract showed protection at a dose of 100 mg/kg body weight. The doses of the extract of selected for remaining studies were based on pilot studies, animal model used, and so forth. These findings suggest that C. asiatica extract possesses potential anticonvulsant, antioxidant, and central nervous system depressant actions.

Preliminary Pharmacological Screening of Benincasa hispida Cogn

Objective :To carry out the preliminary pharmacological screening of methanolic extract of fruit of Benincasa hispida Cogn. Materials and methods : The extract was tested for effect on general pharmacological effects like spontaneous motor activity, muscle relaxant activity, antihistaminic effect and effect on barbiturate induced hypnosis. Results : The extract caused reduction in spontaneous motor activity with no muscle relaxant activity. The extract significantly potentiated the barbiturate induced hypnosis, and showed significant antihistaminic activity. Conclusion : The methanolic extract of fruit of Benincasa hispida has antihistaminic activity and could be further explored.

Semi-quantitative RT-PCR analysis of environmental influence on P450scc and PNMT mRNA expression in rat adrenal glands

Environmental influence on brain function, particularly spatial learning and memory, has been extensively investigated, but little is known about the influence of environmental conditions on the functions of peripheral organs. In the present study, the effects of different housing conditions on the steady-state levels of mRNAs encoding cholesterol side-chain cleavage enzyme (cytochrome P450scc) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands was examined to investigate the environmental influence on both adrenocortical and adrenomedullary functions. Behavioral changes of the animals housed in different conditions were first examined to assess the relevance of environmental manipulation used. In consistent with previous findings, housing of the animals in enriched conditions resulted in the significant reduction of spontaneous motor activity (locomotor activity and rearing) in comparison with housing in isolated conditions, thus indicating the relevance of housing conditions used in this work for investigating the environmental influence on adrenal function. Then, the effects of these housing conditions on P450scc and PNMT mRNA levels in adrenal glands were examined using semi-quantitative RT-PCR method. In comparison with the isolated group, the enriched group showed significantly higher levels of P450scc mRNA. In contrast, PNMT mRNA levels in the enriched group were significantly lower than those in the isolated group. These results propose the possibility that the environmental conditions may cause differential alterations in adrenocortical and adrenomedullary functions, although their possible association with behavioral changes still remains to be elucidated.

Neuropharmacological effect of the aqueous extract of Sphaeranthus senegalensis in mice

Effects of the aqueous extract of Sphaeranthus senegalensis Vaill. (Family: Compositae) were studied on spontaneous motor activity, exploratory behaviour, rota-rod performance and pentobarbital sleeping time in mice. Preliminary phytochemical evaluation and acute toxicity (LD 50) values were also studied. The extract (50 and 100 mg/kg p.o.) produced reduction in spontaneous motor activity, exploratory behaviour and motor coordination and prolonged pentobarbital sleeping time. Glycosides, saponins and tannins were shown to be present in the extract. The i.p. LD 50 in mice was 2735.61 and 5000 mg/kg orally. The results suggest that the aqueous extract of S. senegalensis contains some active principles, which may be sedative in nature.

Neuropharmacology of an Extract derived from Convolvulus microphyllus

Neuropharmacological activities of the methanol extract of the whole plant of Shankhapushpi, Convolvulus microphyllus Sieb ex Spreng (Convolvulaceae), were studied in experimental animals. The extract was found to produce alterations in the general behaviour pattern, reduction in spontaneous motor activity, hypothermia, potentiation of pentobarbitone-sleeping time, reduction in exploratory behavioural pattern, and suppression of aggressive behaviour. The extract also showed an inhibitory effect on conditioned avoidance response and antagonism to amphetamine toxicity. These findings explicitly suggest that the whole plant extract of C. microphyllus possesses a potential CNS-depressant activity.

Decrease in spontaneous motor activity and in brain lipid peroxidation in manganese and melatonin treated mice.

In the present study, we have evaluated whether melatonin (MEL) modulates Mn-induced decrease in spontaneous motor activity (SMA) and lipid peroxidation, estimated as malondialdehyde (MDA) formation, in several brain regions. In mice treated with manganese a decrease in SMA after 2 weeks of treatment was observed. In the group treated with Mn+MEL a significant greater reduction in SMA was detected at 4 weeks. MDA levels were reduced in both MEL and Mn treated mice. In the animals treated with MEL + Mn a higher reduction in MDA levels was observed. These results suggest that MEL modulates the effect of Mn on SMA and brain lipid peroxidation.

The effects of globus pallidus lesions on dopamine-dependent motor behaviour in rats

Motor effects of bilateral lesions of the globus pallidus induced by quinolinic acid (30 and 60 nmol in 0.5 μl) were investigated in rats. Globus pallidus lesions with 60 nmol quinolinic acid produced a significant reduction of spontaneous motor activity measured by a reduced locomotor activity in an open field and by a reduced sniffing activity in an experimental chamber. In addition, d-amphetamine (1 mg/kg, i.p.)-induced hyperlocomotion and d-amphetamine (3 mg/kg, i.p.)-induced stereotyped sniffing were significantly reduced in animals with quinolinic acid lesions (60 nmol). Globus pallidus lesions with 60 nmol quinolinic acid potently reversed catalepsy induced by systemic administration of the dopamine D 1 receptor antagonist SCH23390 (0.75 and 1 mg/kg, i.p.) or the dopamine D 2 receptor antagonist raclopride (1.25 and 5 mg/kg, i.p.), while lesions with 30 nmol quinolinic acid exerted anti-cataleptic effects which were only partly significant. In line with current models of basal ganglia functions, these findings indicate that inactivation of the globus pallidus reduced spontaneous motor activity and motor hyperactivity after dopamine receptor stimulation. However, the present data also demonstrate that inactivation of the globus pallidus reversed motor hypoactivity induced by a blockade of dopamine D 1 and D 2 receptors. Therefore, a more complex functional model of the globus pallidus is required to account for the opposite effects on motor behaviour observed after lesions of this basal ganglia nucleus.