Cataleptic Scores Research Articles

Evaluation of psychopharmacological activity of ethyl acetate extract of Sarcostemaacidum (ROXB).voigt

Herbal medicines are gaining growing interest because of their cost-effective, eco-friendly attributes and true relief from disease condition. Sarcostemaacidum was documented in many folklore practices for various psychiatric conditions. It has been dealt with in detail in “SHRUSHRUTHA SAMHITHA”. Ethyl acetate extract of the whole plant Sarcostemaacidum (EASA) was evaluated for psychopharmacological effects, anti-psychotic, anxiolytic and CNS inhibitory activity. Anti-psychotic effects of EASA was assessed by condition avoidance response and Cataleptic scoring test using pole climbing and Bar test respectively. Elevated Plus maze (EPM) and Hole Board Apparatus (HBA) was employed for the anxiolytic activity while actophotometer was used to assess the CNS inhibitory activity. EASA (650mg/kg), haloperidol (5mg/kg) and 1% CMC was administered to the test,standard and control group respectively for Antipsychotic activity, while for anxiolytic and CNS depressant studies test, standard and control group receive EASA(650mg/kg), diazepam (2mg/kg) and 1% CMC respectively. It was found that EASA significantly enhance the latency period to climb the pole and the cataleptic score which indicates its suppression on CAR activity, which clearly confirms its anti psychotic activity, might be due to blockade of dopaminergic pathway. It was observed that EASA at a dose of 650mg/kg significantly increases the no. of entries in to the open arm in EPM as well as no. of head poking in HBA, which reflects its increase in exploratory behaviour which indicates the anxiolytic activity. Reduction in the locomotor activity in actophotometer indicates CNS depressant property of the drug.

Effect of hydro-alcoholic root extract of Plumbago zeylanica l alone and its combination with aqueous leaf extract of Camellia sinensis on haloperidol induced parkinsonism in wistar rats.

Herbal medicines have been used to treat PD in ancient medical systems in Asian countries such as India, China, Japan and Korea based on their own anecdotal or experience-based theories. Mucuna pruriens commonly known asvelvet beans, or cow itch, are used in case of spasms associated with Parkinsonism. To investigate the antiparkinsonism activity of hydro alcoholic root extract of P. zeylanica L (PZE) aloneand its combination withaqueous extract of C. sinensis leaves (AECS) in Haloperidol induced model. Parkinsonism (PD) was induced by intraperitoneal administration of Haloperidol (1 mg/kg). The extracts/drugs being tested were administered orally (p.o) 60 min prior to the administration of the Haloperidol. Catalepsy was measured using the metal bar test. Haloperidol induced a time dependent increase in cataleptic score in rats, as compared to vehicle treated groups. All the groups ie L-dopa + carbidopa (syndopa), hydro-alcoholic extract of P. zeylanica alone and its combination with C. sinensis showed significantly (P<0.001) lower scores of catalepsy at all time periods as compared to Haloperidol. Results were analyzed by one way ANOVA followed by Dunnet's multiple comparison tests. It is concluded that P. zeylanica alone and its combination with C. sinensis exert a protective effect against PD, while bi-herbal extracts showed more significant protective effect. Hence it may offer a safer therapeutic approach to the treatment of PD and drug induced dyskinesia.

Evaluating the effects and safety of intravenous lipid emulsion on haloperidol-induced neurotoxicity in rabbit.

There are many reports on the effect of intravenous lipid emulsion (ILE) as an antidote in drugs related toxicities. We determined the effects of ILE on neurotoxicity of haloperidol (HA), a highly lipophilic antipsychotic, as a model of antipsychotics poisoning. We used six groups of five male rabbits. Two groups received distilled water intravenously followed by infusions of either 18 mL/kg of normal saline or ILE 20%, after 30 minutes. The third group received 18 mL/kg of normal saline after HA (2.6 mg/kg) administration. The three other groups received ILE 20% solution (6, 12, and 18 mL/kg) following HA injection. Catalepsy scores, temperature, pupil size, and mortality rate were measured at 0, 0.5, 1, 2, 3, 4, 8, and 24 hours after HA administration began. Blood and tissue samples were taken from all animals at 24 hours or at death time for biochemical, cell count, and pathological studies. ILE reversed cataleptic scores, miotic pupils, and hypothermia of HA intoxication much faster than normal saline (P < 0.001). Biochemical complications and mortality rate of the animals were significantly higher in the HA + 18 mL/Kg ILE group. ILE reversed sings of HA neurotoxicity; however, synergistic effect of high dose of ILE and HA increased complications and mortality.

Evaluation of psychopharmacological activity of ethyl acetate extract of Sarcostema acidum (Roxb).voigt

Herbal medicines are gaining growing interest because of their cost- effective, eco- friendly attributes and true relief from disease condition. Sarcostemma acidum was documented in many folklore practices for various psychiatric conditions. It has been dealt with in detail in “SHRUSHRUTHA SAMHITHA”. Ethyl Acetate Extract of the whole plant Sarcostemma acidum (EASA) was evaluated for psychopharmacological effects, Anti Psychotic, Anxiolytic and CNS inhibitory activity. Anti psychotic effects of EASA was assessed by Condition Avoidance Response and cataleptic Scoring test using pole climbing and Bar test respectively. Elevated Plus maze (EPM) and Hole Board Apparatus (HBA) was employed for the anxiolytic activity while Actophotometer was used to assess the CNS inhibitory activity. EASA (650mg/kg), Haloperidol (5mg/kg) and 1% CMC was administered to the test, standard and control group respectively for Antipsychotic activity, while For Anxiolytic and CNS depressant studies test, standard and control group receive EASA (650mg/kg), Diazepam (2mg/kg) and 1% CMC respectively. It was found that EASA significantly enhance the latency period to climb the pole and the cataleptic score which indicates its suppression on CAR activity, which clearly confirms its Anti Psychotic activity, might be due to blockade of dopaminergic pathway. It was observed that EASA at a dose of 650mg/kg significantly increases the no: of entries in to the open arm in EPM as well as no: of head poking in HBA, which reflects its increase in exploratory behaviour which indicates the anxiolytic activity. Reduction in the loco motor activity in actophotometer indicates CNS depressant property of the drug.

Effect of Rosiglitazone, a PPAR‐γ Ligand on Haloperidol‐Induced Catalepsy

Rosiglitazone (Ros) is a commonly prescribed insulin-sensitizing drug with a selective agonistic activity on the peroxisome proliferator-activated receptor-gamma (PPAR-γ). Rosiglitazone, currently approved for use in type II diabetes, was recently shown to cross the blood–brain barrier in mice, suggesting that it might be suitable for testing neuroprotective effects of PPAR-γ agonists in the CNS. Moreover, the presence of PPAR-γ has been detected both in neuronal and glial cells 1. By binding to DNA on promoter regions, PPAR-γ can regulate the expression of several genes, including inflammatory cytokines, TNF-α, COX, iNOS. Furthermore, Ros attenuated the striatal dopaminergic neurodegeneration by anti-inflammatory mechanism, which is relevant to the cataleptic state 2. The aim of this study was therefore to investigate the effect of the Ros on motor symptoms in an animal model of haloperidol (HAL)-induced catalepsy. Adult male Swiss albino mice (25–30 g) that were obtained from Himachal Institute of Pharmacy, Paonta Sahib (H.P), India, were used. The study was approved by the Institutional Animal Ethics Committee. The mice were maintained at 27°C with 12:12 h light-dark cycle for a period of 7 days prior to the study. They were fed with standard rat chow and water ad libitum. The animals were divided into six groups (n = 6). Group I served as control receiving normal saline, Group II served as negative control receiving HAL 2 mg/kg, Group III served as standard receiving Scopolamine 1.0 mg/kg + HAL 2 mg/kg. Group IV and V received Ros 25 and 50 mg/kg + HAL 2 mg/kg, while Group VI received Ros 50 mg/kg alone. All the drugs were administered orally for 15 days except HAL. Haloperidol was given to the appropriate groups on fifth, tenth, and fifteenth day. The Scopolamine or the Ros was given 30 min prior to the administration of the HAL, according to the individual groups. Catalepsy was assessed by means of a standard bar test on every fifth, tenth, and fifteenth day of the drug treatment, as shown in Table 1. The time duration for which the mouse sustained an imposed position with both the front limbs extended and resting on a 4-cm-high wooden bar (1.0 cm diameter) was measured. The end point of the catalepsy was considered to occur when the mice removed both the front limbs from the bar or if the mice moved its head in an exploratory manner. A cut-off time of 300 seconds was applied. All the observations were made between 14.00 and 16.00 h. The maintenance of the imposed posture for a minimum of 20 seconds was considered to be cataleptic. However, the highest time duration of immobility was noted for all animals. On the fifteenth day, cervical dislocation method was used to sacrifice the animals after recording the immobility score. The assay of super oxide dismutase enzyme (SOD) estimates the ability of the enzyme to inhibit the auto-oxidation of pyrogallol. The units of the SOD enzyme were expressed in milligrams of the total protein 3, 4. The brain isolated from the individual mouse was homogenized (20 w/v) in 10 mM phosphate buffer solution with a pH of 7.8. The homogenate was centrifuged, and 0.1 mL of the homogenate (1:10 dilution) was used for the determination. Table 1 shows that the administration of Scopolamine and both doses of the Ros showed significantly (P < 0.05 and P < 0.01) lower cataleptic scores than in the control group in a dose and time-dependent manner. An elevated SOD activity in the mice brain was observed in the HAL-treated group. The scopolamine and Ros (25 and 50 mg/kg) showed a significant (P < 0.01 and P < 0.001) reduction in SOD activity at both doses with a maximum reduction observed with 50 mg/kg Ros group. Previous studies demonstrated that HAL produced cataleptic effects by mediating the dopamine receptors localized postsynaptically on striatal neurons 5. Super oxide dismutase enzyme is a main factor in oxygen toxicity, constituting as an essential defense against the latter. Reduction in antioxidant enzyme is observed in the presence of free radical quenching agent. Haloperidol administration increases the oxidative stress in the brain tissue 6. The increase in SOD in this study confirms the above hypothesis. This study reveals that the Ros-treated groups significantly in comparison with the scopolamine group reduce (P < 0.05, P < 0.01 and P < 0.001) both oxidative stress and the catalepsy score induced by HAL. This study establishes Ros as a beneficial adjuvant in the treatment of drug-induced extra pyramidal side effects and related disorders. The authors declare no conflict of interest.

Sedative, antiepileptic and antipsychotic effects of Viscum album L. (Loranthaceae) in mice and rats

Ethnopharmacological relevanceViscum album L. is claimed in traditional medical practice, to be useful in the treatment of epilepsy and insomnia in Himachal Pradesh, India. Materials and methodsThe effect of Viscum album L. on epilepsy, psychosis and sedative activity was evaluated in mice and rats using standard procedure. ResultsThe aqueous leaf extract of Viscum album L. prolonged the pentobarbital induced sleeping time and reduced the locomotor activity in actophotometer. This suggests that reduced locomotor activity facilitate GABAergic transmission. In addition the extract reduced MES, INH and PTZ-induced convulsions which suggest that there may be possibility of blocking Na+ channels, opening of Cl−channels or enhancing the GABAergic system. The extract decreased the apomorphine-induced stereotyped behavior and potentiates the HAL-induced cataleptic score which suggests the extract possess antidopaminergic activity. ConclusionThe results obtained in present study suggested that title plant exhibited sedative, antiepileptic and antipsychotic activity in mice and rats.

Study of interaction of nifedipine with haloperidol on conditioned avoidance response and catalepsy in rats

Background: To study the interaction of calcium channel blocker (Nifedipine) with Antipsychotic drug (Haloperidol) on Conditioned avoidance Response and catalepsy in Rats. Methods: Every group consisted of 10 healthy albino rats of either sex. Different groups received Nifedipine (5, 10 &amp; 20 mg/kg, i.p.), Haloperidol (ED 50 -0.2mg/kg for CAR &amp; 0.4mg/kg for catalepsy) alone and combined doses of both drugs. The Antipsychotic effect of drugs was measured by Conditioned avoidance response (CAR) using Cook’s Pole climbing apparatus and Adverse drug effect (Extra pyramidal syndrome) was measured by Catalepsy. Results: 5 mg/kg i.p. of Nifedipine inhibited CAR in 50 % of Rats (compared to control, p &lt;0.001). 10mg/kg i.p. of Nifedipine inhibited CAR in 60% of Rats ( p &lt;0.001) &amp; 20 mg/kg i.p. inhibited CAR in 70% of Rats ( p &lt;0.001). When Nifedipine (5 mg/kg i.p) was combined with Haloperidol ED 50 -0.2mg/kg the CAR was inhibited in 70% of the rats ( p &lt;0.01) and after combining Nifedipine (10mg/kg) with Haloperidol ED 50 -0.2mg/kg the CAR was inhibited in 80% Rats ( p &lt;0.001). Nifedipine at the dose of 5 mg/kg and 10 mg/kg (i.p.) did not induce catalepsy in the rats at any testing time interval. At 20 mg/kg i.p., it produced catalepsy in 2 rats at half hour and in 4 rats at 1 hour and 2 hour testing interval each ( p &lt;0.01). In the dose of 5, 10 and 20 mg/kg, pretreatment with Nifedipine significantly increased Haloperidol induced cataleptic scores at all testing intervals ( p &lt;0.05). Conclusions: Nifedipine blocked CAR. Its higher doses induced catalepsy and it is synergistic with haloperidol in blockade of CAR and catalepsy.

Evaluation of toxicological and antioxidant potential of Nardostachys jatamansi in reversing haloperidol-induced catalepsy in rats

An aqueous root extract from Nardostachys jatamansi was investigated for its antioxidant and anticataleptic effects in the haloperidol-induced catalepsy rat model of the disease by measuring various behavioral and biochemical parameters. Catalepsy was induced by administration of haloperidol (1 mg/kg, ip) in male albino rats. A significant (P < 0.01) reduction in the cataleptic scores were observed in all the drug-treated groups as compared to the haloperidol-treated group; with maximum reduction observed in the Nardostachys jatamansi (250 and 500 mg/kg body weight) administered group. To estimate biochemical parameters: the generation of thiobarbituric acid reactive substances (TBARS); reduced glutathione (GSH) content and glutathione-dependent enzymes; catalase; and superoxide dismutase (SOD), in the brain were assessed. Haloperidol administration increased generation of TBARS and significantly reduced GSH, which were restored to near normal level with the Nardostachys jatamansi treatment. Catalase and SOD levels were also increased to normal levels, having been reduced significantly by haloperidol administration. Our findings of behavioral studies and biochemical estimations show that Nardostachys jatamansi reversed the haloperidol-induced catalepsy in rats. We conclude that the antioxidant potential has contributed to the reduction in the oxidative stress and catalepsy induced by haloperidol administration.

Effect of Withania somnifera root extract on haloperidol‐induced catalepsy in albino mice

The objective of the study was to evaluate the anticataleptic effect of Withania somnifera (WS) extract, on haloperidol-induced catalepsy in albino mice. Catalepsy was induced with haloperidol (1 mg/kg) i.p. in five groups of male albino mice (n = 6). Three groups received Withania somnifera extract (1.7, 4.25, 8.5 mg/kg) respectively, one group received scopolamine (1 mg/kg) and one group received the vehicle (1% gum acacia) orally, 30 min prior to haloperidol administration. Catalepsy was measured by using standard bar test at 30, 60, 90, 120 and 240 min. This constituted the acute study. For the chronic study, the drugs were administered for 6 more days. Catalepsy was again measured on day 7. Animals were then sacrificed by cervical dislocation and superoxide dismutase (SOD) activity was estimated in the brain. In this study, Withania somnifera extract treated groups showed a dose dependent reduction in cataleptic scores, both in the acute and chronic study. The SOD activity in brain was also found to be lowered in the WS (4.25 mg, 8.5 mg/kg) treated groups. In conclusion, Withania somnifera was found to be more efficacious than scopolamine in reversing haloperidol induced catalepsy. A clear correlation between the SOD levels and cataleptic scores was observed. We believe that the antioxidant properties of this drug could have contributed to the anticataleptic effect.

Evaluation of the antioxidant potential of NR-ANX-C (a polyherbal formulation) and its individual constituents in reversing haloperidol-induced catalepsy in mice

<b>Objective</b> : To evaluate the possible role of the antioxidant activity of the polyherbal formulation, NR-ANX-C and its individual components in reversing haloperidol-induced catalepsy in Swiss albino mice.<b><br>Materials and Methods</b> : Catalepsy was induced with haloperidol (1 mg/kg <i>i.p</i>) in 13 groups of male albino mice (<i>n</i> = 6 / group). Three groups received NR-ANX-C (10, 25, 50 mg/kg), three groups received <i>Withania somnifera</i> (1.7, 4.25, 8.5 mg/kg), another three groups <i>Ocimum sanctum</i> (1.7, 4.25, 8.5 mg/kg), three other groups <i>Camellia sinensis</i> (3.4, 8.5, 17 mg/kg) and one group received the vehicle (1% <i>Gum acacia</i>) orally, 30 minutes prior to haloperidol administration, for a duration of seven days. Animals were sacrificed on the seventh day and superoxide dismutase (SOD) activity was estimated in the brain.<b><br>Results</b> : A significant (<i>P </i>< 0.01) reduction in the cataleptic scores was observed in all the drug-treated groups as compared to the control, with maximum reduction in the NR-ANX-C 25 mg/kg group. Similarly, a reduction in SOD activity was observed in the NR-ANX-C-, <i>O. sanctum-</i> and the <i>W. somnifera</i>-treated groups. An increase in SOD activity was observed in the <i>C. sinensis</i>-treated groups.<br><b> Conclusion</b> : With the exception of <i>C. sinensis</i>, the antioxidant potential of NR-ANX-C and its individual constituents has contributed to the reduction in the oxidative stress and the catalepsy induced by haloperidol administration.

Differential effects of cyclooxygenase inhibitors on haloperidol-induced catalepsy

Prostaglandins (PGs) might play a role as putative transmitters or as modulators in the central nervous system (CNS). In the present study, haloperidol (1 mg/kg ip)-treated mice showed significant cataleptic behaviour. Naproxen, a nonselective cyclooxygenase (COX) inhibitor, dose-dependently (5 and 10 mg/kg) antagonized the haloperidol-induced catalepsy in mice. Nimesulide, a preferential COX inhibitor, also dose-dependently reduced the cataleptic score in haloperidol treated animals at the first and second hour but not at the third and fourth hour of haloperidol treatment. Rofecoxib, a selective COX-2 inhibitor, did not show any effect on haloperidol-induced catalepsy. The major findings of the present study suggest that PGs might play a significant role in haloperidol-induced catalepsy. The findings of the present study further suggested that COX-1 derived rather than COX-2 derived PGs might play a potential role in haloperidol-induced catalepsy. In conclusions COX inhibitors can be screened as potential drug candidates for the treatment of neuroleptic-induced extrapyramidal side effects (EPS).

Role of nitric oxide in catalepsy and hyperthermia in morphine-dependent rats

The possible involvement of nitric oxide (NO) in morphine-induced catalepsy and hyperthermia was studied in morphine-dependent rats. Four days repeated injection regimen was used to induce morphine dependence, which was assessed by naloxone challenge (0.5 mg kg −1, s.c.). Pretreatment of rats with the NO synthase inhibitor, NG-nitro-l-arginine (l-NA, 8 mg kg −1twice daily, i.p.) potentiated the cataleptic response of morphine as shown by a rightward shift in the morphine-log dose–response curve. Prior treatment of rats with the NO precursor, l-arginine (200 mg kg −1, twice daily, i.p.) abolished the potent effect of l-NA and restored the cataleptic scores to levels similar to those of morphine-dependent rats. The same dose of l-NA significantly blocked morphine-induced hyperthermia at the dose levels of morphine (15–105 mg kg −1) and this effect was reversed by l-arginine. These data provide the first experimental evidence that NO is involved in morphine induced catalepsy and hyperthermia and demonstrated that blockade of NO synthesis may suggest a dangerous interaction with opioids in the control of motor function.

LY 171555-induced catalepsy and defensive behavior in four strains of mice suggest the involvement of different D2 dopamine receptor systems

The D2 dopamine receptor agonist LY 171555 (0.5 to 5 mg/kg) induces dose-dependent catalepsy in C57BL/6, DBA/2 and BALB/c inbred strains of mice. This effect shows marked strain-dependent differences, since the response of C57BL/6 is significantly lower than those presented by the other two inbred strains at all doses tested. In previous studies we have shown that the D2 agonist at doses ranging from 0.5 to 5 mg/kg induces hyperdefensive responses toward nonaggressive opponents in mice of the C57BL/6 and BALB/c but not of the DBA/2 strain. Here we report that the outbred CD1 mice present both cataleptic and hyperdefensive responses when challenged with LY 171555. Forty-five percent of individuals presenting high defensive response and 11% high cataleptic scores. No correlation was found between catalepsy and hyperdefensiveness in CD1 mice following administration of 1 mg/kg of the D2 agonist. These results suggest that D2 receptor stimulation results in different behavioral responses, possibly mediated by different dopaminergic systems, depending on the genetic make up.

Opiate-like actions by intracerebroventricular histamine in mice

Analgesia, catalepsy, head twitch response and hypothermia were observed after intracerebroventricular (i.e.v.) histamine in mice. These symptoms are also seen when morphine and opioid peptides are injected into animals. Histamine has been known to have a role in the tolerance and physical dependence to morphine. In the current study, we examined the opiate-like effects by i.e.v. histamine, especially using catalepsy as an index. The results are as follows: i.e.v. histamine causes cataleptic state in a dose dependent manner (5-1000μg). H1-histamine receptor blocking agents such as pyrilamine, diphenhydramine and cyproheptadine reduced the cataleptic scores in a dose-dependent manner (5-20mg/kg, i.p.). However, H2-histamine receptor blocking agents such as Cimetidine and metiamide have no influence on it (10-100μg, i.e.v.). These results showed the action of histamine is mediated through H1-receptor in the case of catalepsy. Some antidepressants without iprindole reduced the catalepsy and showed their utility as H1-histamine receptor blocking agents. We also investigated certain mechanism of catalepsy in connection with other neurotransmitters. In the central cholinergic system, muscarinic steps are involved in its action since atropine and sparteine reduced the catalepsy, but mecamylamine is without effect. Naloxone reduced the catalepsy (5-10mg/kg). These results showed actions of histamine may stimulate the cholinergic and opioid systems.