Stereotypy In Mice Research Articles

Wortmannin, a potent phosphatidylinositol 3-kinase inhibitor, suppresses methamphetamine-induced stereotyped sniffing and biting, ameliorating the frequency of total stereotypy in mice

Wortmannin, a potent phosphatidylinositol 3-kinase inhibitor, suppresses methamphetamine-induced stereotyped sniffing and biting, ameliorating the frequency of total stereotypy in mice

Crude and Partition Extracts of Newbouldia laevis Leaves Attenuate Excitotoxin-induced Stereotypy in Mice

Aims: This study was designed to investigate the effects of crude ethanol and partition extracts of Newbouldia laevis leaves on excitotoxin-induced stereotypy in mice.
 Place and Duration of Study: The study was carried out in the Laboratory of the Department of Pharmacology and Therapeutics, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria, between July and October, 2020.
 Methodology: Following pretreatment of mice with graded doses (150 - 600 mg/kg b.w) of crude extract (NLE) and partition fractions [n-butanol partition fraction (BPE), n-hexane partition fraction (HPE) and ethylacetate partition fraction (EAPE)] of Newbouldia laevis leaves, stereotypy was induced by the administration of methamphetamine (35 mg/kg b.w) and apomorphine (5mg/kg b.w.), and stereotypy scores were recorded thereafter. The effects of BPE and NLE on catalepsy were also determined. Statistical significance was taken at P<0.05
 Results: In both apomorphine and methamphetamine models, stereotyped behavior was significantly decreased (P<0.05) in the treated mice compared to the control. The degree of protection offered by Newbouldia laevis extracts against excitotoxin-induced stereotypy was in the order: BPE>NLE>EAPE>HPE. In the catalepsy test, BPE (600 mg/kg b.w) significantly potentiated haloperidol-induced catalepsy compared to control (P<0.05). Likewise, NLE significantly increased catalepsy compared to control (P<0.05).
 Conclusion: Findings from this study indicate that crude and partition extracts of Newbouldia laevis leaves attenuated stereotypy in methamphetamine and apomorphine models, and thus could be effective remedy for schizophrenia-like psychosis.

Histamine H3R receptor activation in the dorsal striatum triggers stereotypies in a mouse model of tic disorders

Tic disorders affect ~5% of the population and are frequently comorbid with obsessive-compulsive disorder, autism, and attention deficit disorder. Histamine dysregulation has been identified as a rare genetic cause of tic disorders; mice with a knockout of the histidine decarboxylase (Hdc) gene represent a promising pathophysiologically grounded model. How alterations in the histamine system lead to tics and other neuropsychiatric pathology, however, remains unclear. We found elevated expression of the histamine H3 receptor in the striatum of Hdc knockout mice. The H3 receptor has significant basal activity even in the absence of ligand and thus may modulate striatal function in this knockout model. We probed H3R function using specific agonists. The H3 agonists R-aminomethylhistamine (RAMH) and immepip produced behavioral stereotypies in KO mice, but not in controls. H3 agonist treatment elevated intra-striatal dopamine in KO mice, but not in controls. This was associated with elevations in phosphorylation of rpS6, a sensitive marker of neural activity, in the dorsal striatum. We used a novel chemogenetic strategy to demonstrate that this dorsal striatal activity is necessary and sufficient for the development of stereotypy: when RAMH-activated cells in the dorsal striatum were chemogenetically activated (in the absence of RAMH), stereotypy was recapitulated in KO animals, and when they were silenced the ability of RAMH to produce stereotypy was blocked. These results identify the H3 receptor in the dorsal striatum as a contributor to repetitive behavioral pathology.

Antipsychotic-like activity of scopoletin and rutin against the positive symptoms of schizophrenia in mouse models.

In an earlier report, we demonstrated an antipsychotic-like activity of a methanolic extract of Morinda citrifolia Linn fruit in mouse models and postulated the contribution of its bioactive principles, scopoletin and rutin. Moreover, the antidopaminergic activities of scopoletin and rutin were reported in isolated vas deferens preparations. In the present study, scopoletin and rutin were assessed for antipsychotic-like activity using apomorphine-induced climbing behavior and methamphetamine-induced stereotypy in mice. The results of this study revealed that scopoletin and rutin (0.05, 0.1, 0.5, and 1 mg/kg, p.o.) had a “U-shaped” dose-dependent effect on climbing and stereotyped behaviors induced by apomorphine and methamphetamine, respectively, in mice. A significant reduction in climbing and stereotyped behaviors caused by scopoletin and rutin was observed only at a dose 0.1 mg/kg. This study suggests that scopoletin and rutin can alleviate positive symptoms of schizophrenia only at a specific dose. Further studies evaluating the effects of scopoletin and rutin on animal models for negative symptoms of schizophrenia are required for a novel drug discovery in the treatment of neuropsychiatric diseases.

T-pattern analysis for the study of temporal structure of animal and human behavior: a comprehensive review.

A basic tenet in the realm of modern behavioral sciences is that behavior consists of patterns in time. For this reason, investigations of behavior deal with sequences that are not easily perceivable by the unaided observer. This problem calls for improved means of detection, data handling and analysis. This review focuses on the analysis of the temporal structure of behavior carried out by means of a multivariate approach known as T-pattern analysis. Using this technique, recurring sequences of behavioral events, usually hard to detect, can be unveiled and carefully described. T-pattern analysis has been successfully applied in the study of various aspects of human or animal behavior such as behavioral modifications in neuro-psychiatric diseases, route-tracing stereotypy in mice, interaction between human subjects and animal or artificial agents, hormonal-behavioral interactions, patterns of behavior associated with emesis and, in our laboratories, exploration and anxiety-related behaviors in rodents. After describing the theory and concepts of T-pattern analysis, this review will focus on the application of the analysis to the study of the temporal characteristics of behavior in different species from rodents to human beings. This work could represent a useful background for researchers who intend to employ such a refined multivariate approach to the study of behavior.

Antipsychotic Effect of the Leaves of Stachytarpheta Cayennensis (l.C. Riche) Vahl. Verbenaceae in Mice.

The antipsychotic effect of the extracts of the leaves of Stachytarpheta cayennensis was examined following ethnomedicinal claims for its use in the management of mental illness in Nigeria, Ghana and other tropical parts of the globe. The apomorphine and amphetamine-induced stereotyped behavior models were used in this study to see if the extract or its fractions would abolish the stereotypy in mice. The method of Siqueira et al (1998) was employed in this study and the Kruskal Wallis non parametric ANOVA followed by Mann-Whitney U-test was employed for statistical analysis.The results showed that only the methanolic extract of the leaves of Stachytarpheta cayennesis but none of the fractions thereof prevented stereotyped behavior induced by amphetamine. The extract did not abolish stereotypy induced by apomorphine. The inhibition of amphetamine stereotypy also occurred at only one dose (20 mg/kg, i.p.).The inferences from this study include the fact that for the antipsychotic effect of the leaves of stachytarpheta cayennesis, fractionation would lead to loss of activity. More importantly the methanolic extract of the leaves of Stachytarpheta cayennensis possesses antipsychotic effect and this justifies its ethnomedicinal use in the management of mental illness in some regions of the world.Keywords: Antipsychotic; Stachytarpheta cayennensis; amphetamine; apomorphine; stereotypy

Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice

Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine (DA) D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal DA levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. DA D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm histidine decarboxylase deficiency as a rare cause of TS and identify HA-DA interactions in the basal ganglia as an important locus of pathology.

The selective μ opioid receptor antagonist β-funaltrexamine attenuates methamphetamine-induced stereotypical biting in mice

We investigated whether pretreatment with opioid receptor antagonists affected methamphetamine (METH)-induced stereotypy in mice. Pretreatment of male ICR mice with naloxone, a relatively non-selective opioid receptor antagonist, significantly attenuated the total incidence of METH-induced stereotypical behavior compared with saline vehicle-pretreated subjects. Furthermore, the distribution of METH-induced stereotypical behavior was affected by naloxone administration. Thus, METH-induced stereotypical sniffing and persistent locomotion were significantly increased by naloxone treatment while stereotypical biting was reduced. One way to interpret this pattern of effects is that pretreatment with naloxone appeared to produce a shift in the dose–response curve for METH. Thus, while the more intense forms of oral-facial stereotypies were reduced, increased persistent locomotion was observed in mice given naloxone followed by METH. The selective μ opioid receptor antagonist β-funaltrexamine, but not nor-binaltorphimine (a κ-selective antagonist) nor naltrindole (a δ-selective antagonist), mimicked the effect of naloxone. These observations suggest that opioid receptor antagonists may attenuate METH-induced stereotypical biting in mice via μ opioid receptors, and suggest that antagonism of this system may be a potential therapeutic approach to reducing some deleterious effects of METH use and perhaps in the treatment of some forms of self-injurious behavior.

Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate

Heparan sulfate regulates diverse cell-surface signaling events, and its roles in the development of the nervous system recently have been increasingly uncovered by studies using genetic models carrying mutations of genes encoding enzymes for its synthesis. On the other hand, the role of heparan sulfate in the physiological function of the adult brain has been poorly characterized, despite several pieces of evidence suggesting its role in the regulation of synaptic function. To address this issue, we eliminated heparan sulfate from postnatal neurons by conditionally inactivating Ext1, the gene encoding an enzyme essential for heparan sulfate synthesis. Resultant conditional mutant mice show no detectable morphological defects in the cytoarchitecture of the brain. Remarkably, these mutant mice recapitulate almost the full range of autistic symptoms, including impairments in social interaction, expression of stereotyped, repetitive behavior, and impairments in ultrasonic vocalization, as well as some associated features. Mapping of neuronal activation by c-Fos immunohistochemistry demonstrates that neuronal activation in response to social stimulation is attenuated in the amygdala in these mice. Electrophysiology in amygdala pyramidal neurons shows an attenuation of excitatory synaptic transmission, presumably because of the reduction in the level of synaptically localized AMPA-type glutamate receptors. Our results demonstrate that heparan sulfate is critical for normal functioning of glutamatergic synapses and that its deficiency mediates socio-communicative deficits and stereotypies characteristic for autism.

Cage-induced stereotypies in female ICR CD-1 mice do not correlate with recurrent perseveration

Stereotypies are repetitive, unvarying, apparently purposeless behavioural patterns. They develop in animals kept in barren environments and are highly prevalent in laboratory mice ( Mus musculus), yet their underlying mechanisms have remained elusive. In humans, stereotypies are associated with several psychiatric disorders and are thought to reflect dysfunction of inhibition of motor programs mediated by the corticostriatal circuitry, resulting in recurrent perseveration (=inappropriate repetition of behavioural responses). Several studies in captive animals of different species have reported a correlation between stereotypy performance and perseverative behaviour, indicating a similar dysfunction. To examine whether stereotypies in mice correlate with recurrent perseveration and whether they are causally related, we raised 40 female ICR CD-1 mice in either barren or enriched cages from three to either six or 16 weeks of age (2 × 2 factorial design) and assessed stereotypic behaviour in the home cage and recurrent perseveration on a two-choice guessing task. Enrichment significantly reduced stereotypic behaviour both at six and 16 weeks of age and recurrent perseveration increased with age. Although enriched housing reduced the number of repetitions in the guessing task significantly, there was no clear evidence for an effect on recurrent perseveration, and recurrent perseveration did not correlate positively with stereotypy level. These findings indicate either that this test did not measure recurrent perseveration or that cage stereotypies in these mice do not reflect behavioural disinhibition as measured by recurrent perseveration.

Methamphetamine-induced stereotypy in mice: Regulation by L-histidine

Methamphetamine-induced stereotypy in mice: Regulation by L-histidine

Sigma1 receptor antagonists determine the behavioral pattern of the methamphetamine-induced stereotypy in mice

The effects of sigma receptor antagonists on methamphetamine (METH)-induced stereotypy have not been examined. We examined the effects of sigma antagonists on METH-induced stereotypy in mice. The administration of METH (10 mg/kg) to male ddY mice induced stereotyped behavior consisting of biting (90.1%), sniffing (4.2%), head bobbing (4.1%), and circling (1.7%) during an observation period of 1 h. Pretreatment of the mice with BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol; 1, 5, and 10 mg/kg), a non-specific sigma receptor antagonist, significantly increased METH-induced sniffing (19.2%, 30.5%, and 43.8% of total stereotypical behavior) but decreased biting (76.6%, 66.9%, and 49.3% of total stereotypical behavior) in a dose-dependent manner. This response was completely abolished by (+)-SKF 10,047 ([2S-(2alpha,6alpha,11R)]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol; 4 and 10 mg/kg), a putative sigma(1) receptor agonist, and partially by PB 28 (1-cyclohexyl-4-[3-(1,2,3,4-tetrahydro-5-methoxy-1-naphthalen-1-yl)-n-propyl]piperazine; 1 and 10 mg/kg), a putative sigma(2) receptor agonist. The BMY 14802 action on METH-induced stereotypy was mimicked by BD 1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine; 10 mg/kg), a putative sigma(1) receptor antagonist, but not by SM-21 ((+/-)-tropanyl 2-(4-chlorophenoxy)butanoate; 1 mg/kg), a putative sigma(2) receptor antagonist. The BD 1047 effect on METH-induced stereotypy was also abolished completely by (+)-SKF 10,047 and partially by PB 28. The overall frequency of METH-induced stereotypical behavior was unchanged with these sigma receptor ligands, despite the alteration in particular behavioral patterns. The BMY 14802 action on METH-induced stereotypy was unaffected by pretreatment with centrally acting histamine H(1) receptor antagonists (pyrilamine or ketotifen, 10 mg/kg), suggesting that these effects are independent of histamine H(1) receptor signaling systems. In summary, modulation of central sigma(1) receptors alters the pattern of METH-induced stereotypy, producing a shift from stereotypical biting to stereotypical sniffing, without affecting the overall frequency of stereotypical behavior.

Blockade of brain histamine metabolism alters methamphetamine-induced expression pattern of stereotypy in mice via histamine H 1 receptors

The administration of methamphetamine (METH, 10 mg/kg, i.p.) to male ICR mice induced stereotyped behavior consisting of nail and/or wood chip biting (86.0%), continuous sniffing (12.0%), head bobbing (1.1%), and circling (1.0%) during the observation period of 1 h. Pretreatment of the mice with metoprine (2, 10, and 20 mg/kg, i.p.), a selective inhibitor of histamine N-methyltransferase (HMT), which metabolizes histamine in the brain, significantly increased and decreased METH-induced continuous sniffing (20.5, 51.3, and 80.3%) and nail and/or wood chip biting (77.4, 45.3, and 14.2%), respectively, in a dose-dependent manner. The hypothalamic contents of histamine and its metabolite N τ-methylhistamine were significantly increased and decreased by metoprine (10 mg/kg, i.p.), respectively. The metoprine action on METH-induced behavior was completely abolished by pyrilamine (10 and 20 mg/kg) and ketotifen (10 mg/kg), selective, centrally acting histamine H 1 receptor antagonists, but not by fexofenadine (20 mg/kg), zolantidine (10 mg/kg) and thioperamide (10 mg/kg), a peripherally acting histamine H 1 receptor antagonist and a selective, brain-penetrating antagonist for histamine H 2 and H 3 receptors, respectively. The metoprine action was mimicked by SKF 91488 (100 μg/animal, i.c.v.), another HMT inhibitor, and the action of SKF 91488 was also blocked by pyrilamine. The frequency of the expression of METH-induced total stereotypic patterns was unchanged after metoprine pretreatment. Mice pretreated with metoprine displayed no anxiety-like behavior in the elevated plus maze test. These results suggest that brain histamine, increased by agents such as metoprine and SKF 91488, binds to histamine H 1 receptors in the brain, resulting in the modulation of dopaminergic transmission associated with stereotyped behavioral patterns induced by METH.

Effect of GNTI, a kappa opioid receptor antagonist, on MK-801 -induced hyperlocomotion and stereotypy in mice

To examine the effect of GNTI [5'-guanidinyl-17-(cyclopropylmethyl)-6,7- dehydro-4,5alpha-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan], a selective antagonist for the kappa opioid receptor, in the MK-801 (dizocilpine maleate)-induced behavioral model of psychosis in schizophrenia as a way to explore the involvement of the kappa opioid receptor in modulating psychotic symptoms of schizophrenia. Two doses of MK-801 (0.3 mg/kg and 0.6 mg/kg) were administered by systemic injection in mice to induce psychosis-like behavior as a rodent schizophrenia model, preceded by an injection of different doses of GNTI. Both locomotion and stereotypy were measured as the behavioral endpoints for quantitative analysis. GNTI inhibited MK-801-induced hyperlocomotion and stereotypy. In particular, GNTI showed differential modulation of stereotypy induced by 0.3 mg/kg vs 0.6 mg/kg MK-801. Antagonism of kappa opioid receptors attenuates MK-801-induced behavior, suggesting a potential involvement of the kappa opioid receptor in psychosis-like symptoms of schizophrenia. GNTI appears to be a useful pharmacological tool to explore the kappa opioid receptor function in vivo.

An organic selenium compound attenuates apomorphine-induced stereotypy in mice

Selenium compounds display neuroprotective activities mediated at least in part by their antioxidant actions. Oxidative damage has been implicated in psychiatric disorders including schizophrenia and bipolar disorder, and an alteration in expression of selenium-binding protein-1 ( SELENBP-1) has been recently reported in both the blood and brain of schizophrenic patients. In the present study we examined the effects of the organic selenium compound 3′3-ditrifluoromethyldiphenyl diselenide [(F 3CPhSe) 2] on apomorphine-induced stereotypy in mice, an animal model of psychosis. Systemic administration of (F 3CPhSe) 2 at the highest dose used (25.0 μmol/kg in a 10.0 ml/kg injection volume) significantly reduced apomorphine-induced stereotyped behaviors. A series of control experiments showed that the same dose of (F 3CPhSe) 2 did not affect open-field behavior, habituation, or aversively motivated memory. The results indicate that organic selenium compounds should be further investigated as agents with possible antipsychotic properties.

Effects of Monoamine Oxidase Inhibitors on Methamphetamine-Induced Stereotypy in Mice and Rats

In male ICR mice, a single intraperitoneal administration of methamphetamine (METH) (10 mg/kg) induced stereotyped behavior such as continuous sniffing, circling, and nail biting, reaching a plateau level 20 min after the injection. Subcutaneous pretreatment with clorgyline, a monoamine oxidase (MAO)-A inhibitor, at a dose of 0.1 mg/kg 2 h prior to the drug challenge significantly decreased the initial (first 20 min) intensity of stereotypies and increased the latency to onset. The effect was not observed with either higher doses of clorgyline (1 and 10 mg/kg) or l-deprenyl, a MAO-B inhibitor, at doses of 0.1-10 mg/kg. In male Wistar rats, the inhibitory effect of clorgyline on METH-induced stereotypy was not observed. Pretreatment of the mice with clorgyline (0.1 mg/kg) had no effect on apparent serotonin and dopamine turnover in the striatum, although the higher doses of clorgyline (1 and 10 mg/kg) significantly decreased the turnover. These results suggest that a low dose of clorgyline tends to increase the latency and decrease the intensity of stereotypies induced by METH in a dopamine metabolism-independent manner in mice.

2-Phenylethylamine in combination with l-deprenyl lowers the striatal level of dopamine and prolongs the duration of the stereotypy in mice

2-Phenylethylamine (PEA)-induced stereotypy in rodents is suggested to model psychotic symptoms of schizophrenia. It is reported that PEA induces dopamine release in the striatum in vivo and in vitro. The present study analyzed the PEA-induced stereotypy and possible associated brain dopamine metabolism in mice. Using male ICR mice treated with a combination of PEA (100 mg/kg, i.p.) and increasing doses of l-deprenyl (0–10 mg/kg, s.c.), we examined (1) the behavioral profile of stereotypy (rating the scores), and (2) the tissue levels of dopamine and its metabolites by high-performance liquid chromatography. The stereotypic scores reached a plateau level at 10 min which lasted until 30 min after a single administration of 100 mg/kg PEA. The stereotyped behavior completely disappeared 45 min after PEA administration. Pretreatment with l-deprenyl (0.1, 1, and 10 mg/kg, s.c.) dose-dependently prolonged the duration of PEA-induced stereotypy. Notably, pretreatment with l-deprenyl dose-dependently increased the continuous sniffing. Treatment with PEA in combination of l-deprenyl (1 and 10 mg/kg) significantly reduced the level of dopamine in the region of the striatum and nucleus accumbens, compared with control animals. These results suggest that PEA in combination with l-deprenyl prolonged the duration of the stereotypy (particularly, continuous sniffing) while reducing the striatal level of dopamine.

Effects of intrastriatal administration of selective dopaminergic ligands on spontaneous stereotypy in mice

Abnormal repetitive behaviors are often associated with specific developmental, genetic, and neuropsychiatric disorders. Repetitive motor behaviors, often referred to as stereotypies, have been studied extensively as they can be readily induced by certain drugs (e.g., amphetamine). Recent work has shown, however, that such drug-induced models of stereotypy may not accurately reflect the neurobiological perturbations responsible for the spontaneous manifestation of these behaviors. The present study employed the deer mouse model of spontaneous and persistent stereotypy to evaluate the capacity of several selective dopaminergic agonists (apomorphine, SKF81297, and quinpirole) to exacerbate levels of spontaneously emitted stereotypic topographies when administered intrastriatally. Additionally, the effects of intrastriatal administration of the D2R antagonist raclopride on the expression of spontaneous stereotypic jumping were evaluated. No induction or exacerbation of stereotypy was observed following administration of the selective D1- or D2- receptor agonists, and the mixed agonist apomorphine induced hyperlocomotion and excessive grooming but failed to exacerbate spontaneous stereotypy. Thus, a dissociation was observed between spontaneously emitted and drug-induced stereotypy, suggesting significant limitations to the use of dopamine agonist-induced stereotypy as a model of clinical stereotyped movement disorder. Furthermore, an unexpected and statistically significant (P<.05) potentiation of locomotor activity was observed following intrastriatal raclopride administration, suggesting major alterations to the modulatory characteristics of the striatal dopaminergic system in these spontaneously stereotypic animals.

Postsynaptic dopamine (D 2)-mediated behavioural effects of high acute doses of artemisinin in rodents

Artemisinin or qinghaosu is the active principle of quinghao ( Artemisia annua L.) developed from Chinese traditional medicine, which is now widely used around the world against falciparum malaria. Behavioural effects of high acute doses of artemisinin were studied on spontaneous motor activity (SMA), exploratory behavior, apomorphine-induced stereotype behavior and pentobarbital sleeping time in mice and rats in order to provide additional evidence on its safety profile on the central nervous system (CNS). Effects of the drug on bromocriptine-induced hyperactivity in short term reserpinised mice were also evaluated. Intraperitoneal (i.p.) injection of artemisinin at doses of 50 and 100 mg/kg, significantly ( P<0.05) reduced the SMA in mice, prolonged the pentobarbital sleeping time in rats, and attenuated the apomorphine-induced stereotypy in mice. Mice pretreated with reserpine, showed a significant decrease in locomotor activity compared to the saline-treated group. Bromocriptine, a D 2 receptor agonist, induced locomotor activity in mice pretreated with reserpine which was attenuated by artemisinin. The results suggest that artemisinin possesses sedative property, which may be mediated via postsynaptic dopamine (D 2) receptor in the CNS.

Central nervous system activity of the methanol extract of Ficus platyphylla stem bark

The central nervous system (CNS) activity of the methanolic extract of Ficus platyphylla stem bark was studied on locomotor activity, pentobarbital sleeping time, exploratory behaviour, amphetamine-induced hyperactivity, apomorphine-induced stereotypy, active-avoidance and performance on tread mills (rota-rod), using mice and rats. The results revealed that the extract significantly reduced the locomotor and exploratory activities in mice, prolonged pentobarbital sleeping time in rats, attenuated amphetamine-induced hyperactivity and apomorphine-induced stereotypy in mice, dose-dependently. The extract significantly suppressed the active-avoidance response in rats, with no significant effect on motor co-ordination as determined by the performance on rota-rod. The results suggest that the extract may possess sedative principles with potential neuroleptic properties.