Kanji Izumi

Capsaicin-induced neuroparalytic keratitis-like corneal changes in the mouse

A single subcutaneous injection of 12.5-100 mg kg-1 capsaicin to newborn mice produced gross corneal changes. The changes were manifest about three weeks after capsaicin treatment and progressed dose-dependently from slight punctate vesiculations in the epithelium to diffuse edematous opacities and vascularizations in the stroma, followed by recovery in several weeks with or without residual scars. Control newborn mice with vehicle solution did not show any corneal abnormality. The most prominent histopathological feature of the affected corneas was a marked loss of nerve axons in the epithelium with associated disorganization of the epithelium. Similar corneal changes were observed with systemic capsaicin treatment to young or adult mice. The pathogenesis of the capsaicin-induced corneal changes was discussed with reference to the trophic action of the trigeminal nerve.

Corneal lesions induced by the systemic administration of capsaicin in neonatal mice and rats

SummaryFollowing a single subeutaneous injection of capsaicin to neonatal mice, a high incidence of corneal lesions with opacity developed after a long latency. The intensity of the lesions progressed for about 1 month in animals which had received a high dose (50 or 100 mg/kg) of capsaicin. Although the intensity gradually decreased thereafter, 50% of animals still exhibited a visible opacity 6 months after treatment. Similar corneal lesions were also produced in neonatal rats which had been injected with capsaicin. It is suggested that the corneal lesions induced by capsaicin may be due to destruction of the trigeminal nerve.

Postural myoclonus associated with long-term administration of neuroleptics in schizophrenic patients

Postural myoclonus associated with long-term administration of neuroleptics was demonstrated in schizophrenic patients. Sixty patients who had been taking neuroleptics for more than 3 months were investigated for myoclonus and the relationships between postural myoclonus and age, duration of illness, duration of medication, current daily dose, cumulative dose, occurrence of abnormal finger movement, parkinsonism, and tardive dyskinesia were evaluated. Twenty-three patients (38%) showed postural myoclonus when holding the hands forward with the elbow joints flexed at about 90%. Male patients showed a higher incidence of myoclonus than female patients. Patients with myoclonus had been given significantly higher doses of neuroleptics than those without myoclonus. There was a significant correlation between the occurrence of myoclonus and abnormal finger movement. Electromyographic recordings in 7 patients with prominent myoclonus revealed that arrhythmic jerks occurred in the extensor carpi radialis and posterior deltoid muscles and that the jerks on the left and right side were not synchronized. Clonazepam reduced the frequency of the myoclonic activity.

Effects of repeated testing on the incidence of haloperidol-induced catalepsy in mice

Effects of repeated testing on the incidence of haloperidol-induced catalepsy were investigated in mice. The incidence of catalepsy, evaluated with the forelimbs or hindlimbs placed on a standard horizontal bar, increased in three successive tests in mice injected with haloperidol. Catalepsy was not provoked by repeated testing in animals with saline. In a subsequent study, mice were examined for catalepsy in the forelimbs in the first two trials and then in the hindlimbs. In this procedure, the incidence of catalepsy did not increase with repeated testing. These results suggest that repeated testing increases the incidence of haloperidol-induced catalepsy but does not influence the cataleptogenic potency of the drug.

Inhibitory effect of taurine on wet-dog shakes produced by [d-Ala2,MET5] enkephalinamide with reference to effects on hippocampal epileptic discharges

The effects of taurine on wet-dog shakes produced by [D-Ala2,Met5]enkephalinamide (DAME) were investigated in rats. Wet-dog shakes and epileptic discharges in the hippocampus were produced by intraventricular administration of 50 micrograms of DAME. Pretreatment with 10 microliter of taurine, given intraventricularly in a dose of 0.95 mumol, inhibited wet-dog shakes and epileptic discharges in the hippocampus. While the same dose of gamma-aminobutyric acid (GABA) also inhibited the wet-dog shakes, the same dose of L-leucine did not suppress them. These observations indicate that the inhibition of DAME-induced wet-dog shakes by taurine is associated with the suppression of seizure activities in the hippocampus. The possibility that taurine possesses an antagonistic action on opioid peptides is discussed.

Meclofenoxate therapy in tardive dyskinesia: A preliminary report

Tardive dyskinesia seems to occur as a result of diminished cholinergic and enhanced dopaminergic activity in the striatum. Meclofenoxate has been shown to increase cerebral cholinergic activity. To ameliorate the tardive dyskinesia, meclofenoxate was given orally, 600-1200 mg/day, for 6-12 weeks. The effects of the drug were evaluated by scoring the degree of involuntary movement. Among 11 subjects with tardive dyskinesia or dystonia, 4 improved markedly, 1 moderately, 2 slightly, and there was no improvement in 4. One patient with subacute oral dyskinesia, induced by administration of neuroleptics for 1 month, improved markedly. The possibility that meclofenoxate may be effective in dealing with dyskinesias that are induced by neuroleptics warrants further attention.

Upregulation of postsynaptic dopamine receptors in the striatum does not influence haloperidol-induced catalepsy in mice.

The incidence of haloperidol-induced catalepsy was investigated in mice whose postsynaptic dopamine (DA) receptors in the striatum had been upregulated by denervation with 6-hydroxydopamine (6-OHDA). In nonupregulated mice, which were injected with 6-OHDA 4 days before, DA in the striatum fell to 21% of the level found in vehicle-injected mice but [3H]spiperone binding to the membrane of the striatum did not increase. In upregulated mice, which were injected with 6-OHDA 28 days before, DA was at 24% and [3H]spiperone binding increased by 15%. The ED50 values (with 95% confidence limits) for haloperidol-induced catalepsy in nonupregulated mice and that in upregulated mice was 0.40 mg/kg (0.25-0.65 mg/kg) and 0.29 mg/kg (0.16-0.51 mg/kg), respectively. There was no significant difference in the incidence of catalepsy between the two groups of mice. This suggests that the intensity of catalepsy produced by the DA receptor blockade may be unaltered even when the density of receptors increases.

Phenytoin potentiates methamphetamine-induced behavior in mice

We demonstrated that stereotyped behavior and tremor induced by methamphetamine (MA) were potentiated by pretreatment with phenytoin (PNT) in mice. Similar enhancing effects were obtained by pretreatment with carbamazepine. Gas chromatographic study demonstrated that pretreatment with PNT increased MA concentrations in the brain to approximately 2.5 times of control level. The increased MA concentrations were thought to be a major factor for the observed potentiation of MA-induced behavior by PNT. However, all MA-induced behavior were not equally potentiated; tremor was enhanced more than stereotypy. These results suggest that central neuronal mechanisms may also be involved in PNT-potentiated MA-induced behavior in mice.

Modification of the antiepileptic actions of phenobarbital and phenytoin by the taurine transport inhibitor, guanidinoethane sulfonate

We investigated whether chronic administration of guanidinoethane sulfonate, an inhibitor of taurine uptake, could modify the antiepileptic actions of phenobarbital and phenytoin on maximal electroshock seizures in mice. Treatment with 1% guanidinoethane sulfonate decreased the taurine concentration in the brain to 76% of the control value. Under these conditions, neither the severity of tonic convulsions of maximal electroshock seizures nor the threshold for tonic extension caused by electroshock was altered. However, treatment with guanidinoethane sulfonate lessened the antiepileptic actions of phenobarbital and phenytoin on electroshock seizures. The brain concentrations of phenobarbital and phenytoin were unaltered by administration of guanidinoethane sulfonate. The brain concentrations of guanidinoethane sulfonate and total guanidino compounds were unchanged by the injection of either phenobarbital or phenytoin. It is suggested that the observed loss of anticonvulsive potency of phenobarbital and phenytoin may have been related to the decrease in taurine concentration produced by guanidinoethane sulfonate.

Taurine inhibits wet-dog shakes and hippocampal seizures induced by opioid peptides in rats.

Wet dog shakes (WDS) are paroxysmal shudders of head, neck and trunk. This behavior has been observed when dipping animals into cold water (41), application of xylene to the fur (39) and tactile stimulation around ears (1). Pharmacological studies revealed that WDS can be produced by administration of thyrotropin-releasing hormone (9,24,29,41,42), 5-Hydroxytryptamine (3,12), or kainic acid (5,25). WDS are also known as a classical sign of morphine abstinence in rats (40,43). In 1976, Bloom et al. first reported that this shaking behavior was elicited by acute administration of β-endorphln into the lateral ventricle in rats. Similar observations were made in rats with enkephalin (15). In addition, it was found that epileptic discharges were provoked by the intraventricular (icv) injection of opioid peptides and WDS always accompanied the onset of seizure discharges (15,16,37). These findings suggest that there may be an association between electrical seizure activities and WDS.