Anticonvulsant and behavioral actions of triterpene isolated from Rubia cordifolia Linn.

Effect of a triterpene isolated from the acetone soluble part of petroleum ether extract of R. cordifolia was studied on convulsions induced by maximum electro shock (MES), electrical kindling and various chemoconvulsants in rats and mice. The effect of triterpene was also investigated on behavior and gamma-aminobutyric acid (GABA) and serotonin (5-HT) content in mouse brain. Triterpene inhibited seizures induced by MES, electrical kindling, pentylenetetrazol (PTZ), and lithium-pilocarpine. However, seizures induced by strychnine were not inhibited. Triterpene reduced locomotion as well as rearing. Pentobarbitone induced sleep was potentiated and amphetamine induced stereotypy was inhibited. The triterpene was found to possess anxiogenic activity. Brain GABA and 5-HT contents were raised by the compound. The study suggests that the triterpene isolated from R. cordifolia bear a potential for further study.

Haloperidol-induced catalepsy: a model for screening antidepressants effective in treatment of depression with Parkinson's disease.

Incidence of severe depression is very common in Parkinson's disease (PD). Use of antidepressants in such cases is known to improve or worsen the existing PD. However, prediction of the effect of antidepressant on symptoms of PD is limited due to lack of suitable animal model. The present study examines the possibility of using haloperidol-induced catalepsy model in rats for this purpose. Antidepressants showed distinct effect on haloperidol-induced catalepsy, although most of them reduced forced-swimming induced immobility. In general, antidepressants with greater noradrenergic reuptake inhibition (desipramine, imipramine, amitriptyline, nortriptyline, protriptyline and maprotiline) reduced, whereas those with serotonergic reuptake inhibition (fluoxetine and clomipramine) increased haloperidol-induced catalepsy. Mianserin, an atypical antidepressant, and alprazolam, a benzodiazepine receptor analogue had no effect on haloperidol-induced catalepsy. The results suggest that haloperidol-induced catalepsy model in rats needs to be incorporated in the screening procedure when evaluating the utility of antidepressant drugs for the treatment of depression associated with PD.

Neurobehavioral effects of low level fenvalerate exposure in mice.

Effect of oral administration of fenvalerate, a pyrethroid insecticide was studied in different behavioral paradigms in mice. Fenvalerate at 15, 30 and 45 mg/kg dose increased start latency, decreased ambulation and rearing in open-field, increased immobility in tail-suspension test and attenuated haloperidol-induced catalepsy in a dose-dependent manner. The time-course of data shows that these effects of fenvalerate may sustain up to several hours of its oral administration. The study indicates that pyrethroids can cause adverse behavioral effects even after a very low-level exposure. Although, it is difficult to extrapolate these findings directly to behavioral changes in man, they indicate that subtle behavioral dysfunction also occur in humans at exposures which do not cause acute toxicity.

GABAergic agents modify imipramine analgesia.

The influence of GABA agonists and antagonists on analgesic activity of imipramine (IMA, 20 mg/kg, ip) was studied using the hotplate method. Administration of GABAA receptor agonist muscimol (1 mg/kg, ip), GABAB receptor agonist baclofen (3 mg/kg, ip) or GABA-T inhibitor aminooxyacetic acid (25 mg/kg, ip) increased the analgesic effect of IMA. On the other hand pretreatment of GABAA receptor antagonist bicucukline (2 mg/kg ip), GABAB receptor antagonist delta-amino-n-valeric acid (50 mg/kg, ip) or GABA synthesis inhibitor thiosemicarbazide (50 mg/kg, ip) attenuated the IMA analgesia. These results suggest that the analgesic action of IMA may be mediated by functional alteration of a central GABAergic mechanism and/or subsequent stimulation of GABA receptors.

Effect of neuropeptide FMRFamide on immobile behavior in rats.

In the forced swimming induced immobility test, neuropeptide FMRFamide (5-20 micrograms) administered via the intracerebroventricular (icv) route, prolonged immobilization period in rats. On the other hand, immunoneutralization of endogenous FMRFamide by its antiserum (1 microliter, icv) significantly reduced the duration of immobility. Intraperitoneal administration of amitriptyline (3 mg/kg), imipramine (5 mg/kg), fluoxetine (5 mg/kg) or amphetamine (0.5 mg/kg) attenuated FMRFamide-induced prolongation of immobility. Biochemical studies indicated that FMRFamide treatment had significant effects on rat brain monoamines. FMRFamide significantly lowered the brain levels of 5-hydroxytryptamine and norepinephrine in the doses that prolonged the immobility. These results that FMRFamide prolongs the duration of immobility, perhaps by modulating the release of neurotransmitters like 5-hydroxytryptamine and/or norepinephrine.

Stimulation of gastric acid secretion by central administration of FMRFamide in rats.

The possible role of centrally administered tetrapeptide FMRFamide (Phe-Met-Arg-Phe-NH2) on gastric acid secretion in pylorus ligated rats was investigated. Intracerebroventricularly administered FMRFamide stimulated the gastric acid secretion in a dose-dependent manner. This stimulatory effect was abolished by vagotomy and atropine pretreatment. The presence of FMRFamide in rat brain and the ability of FMRFamide to stimulate gastric acid secretion suggest that FMRFamide plays a physiological role in brain modulation of gastric acid secretion.

Modification of tricyclic antidepressant analgesia by calcium channel blockers.

The influence of calcium channel blockers (CCB) on the analgesic activity of tricyclic antidepressants (TCA) was examined using hot plate (thermal) and writhing (chemical) method. Intraperitoneal injections of TCA, imipramine and amitriptyline or CCB viz: verapamil, nifedipine, nicardipine and cinnarizine per se produced analgesia. The Analgesic effect of TCA was further enhanced by prior treatment with CCB. The increase in TCA analgesia could not be ascribed to unitary mechanism but could possibly be mediated by opioid and/or nonopioid systems. These results clearly provide an evidence that a combination treatment of CCB and TCA may permit reduction of the TCA doses while treating chronic pain of organic origin.

Influence of fatty acids on pressor responses to catecholamines.

Lauric, Myristic and Palmitic acids had no appreciable effect whereas Stearic, Oleic and Linoleic acids caused some reduction in dog blood pressure. Pressor responses to epinephrine and nor-epinephrine were potentiated whereas the depressor response to isoproterenol was reduced during the infusion of fatty acids in dogs. ACTH alone, which causes mobilization of free fatty acids had no appreciable effect on blood pressure responses to catecholamines, however, its administration followed by salicylate produced marked potentiation of the pressor responses to epinephrine and nor-epinephrine; the depressor response to isoproterenol was reduced.

Effect of Krebs cycle metabolites on frog heart.

All the Krebs metabolites except pyruvate, lactate, acetate and succinate reduced the force and rate of myocardial contractions and also decreased cardiac output in frog. Succinate on the contrary was found to augment the rate and force of heart. The cardiac stimulation produced by epinephrine was reduced by fumarate, malate, oxaloacetate and alpha-oxoglutarate, whereas transaconitate and citrate produced only a slight inhibition. Pyruvate, lactate, acetate and succinate did not alter cardiac response to epinephrine.