Protective effect of cyclooxygenase (COX)-inhibitors against drug-induced catatonia and MPTP-induced striatal lesions in rats.

The present study explored the involvement of cyclooxygenase (COX) in the pathophysiology of Parkinson's disease (PD). Further, the protective effect of COX-inhibitors against perphenazine-induced catatonia and 1-methyl-4-phenyl-1, 2, 3, 6-tertahydropyridine (MPTP)-induced striatal lesions in rats was evaluated. Administration of perphenazine (5 mg/kg., i.p.) produced severe catatonia (rigid behavior) in rats; the maximum score reached at 4 h (estimated as 100% AUC) and declined within 24 h. An intrastriatal injection of MPTP produced hypolocomotor activity in rats. Both perphenazine and MPTP produced oxidative stress as demonstrated by increased levels of lipid peroxides, nitrite and decreased antioxidant defense system in the whole brain and striatal region, in particular. Pretreatment with various COX-inhibitors viz. rofecoxib, celecoxib, nimesulide or naproxen offered protection against perphenazine-induced catatonia, the effect was more pronounced with rofecoxib. Rofecoxib and celecoxib (both selective COX-2 inhibitors) also reversed the perphenazine-induced oxidative stress. Further, prior treatment with rofecoxib (8 mg/kg, p.o.) reversed both the behavioral and biochemical changes induced by MPTP. These results suggest that COX-inhibitors particularly, rofecoxib offers protection against drug-induced catatonia and MPTP-induced striatal lesions possibly by modulating dopaminergic neurotransmission and/or oxidative stress.

Increase of serum creatine phosphokinase in catatonia: an investigation in 32 acute catatonic patients.

We investigated serum creatine phosphokinase (CPK) and associated parkinsonic (SEPS) and dyskinetic (AIMS) movements in 32 hospital admitted acute catatonic patients. Thirty-two (N = 24 without neuroleptics on admission) catatonic patients were compared with 32 non-catatonic dyskinetic psychiatric patients, 32 non-catatonic non-dyskinetic psychiatric patients and 32 healthy controls. CPK was significantly higher (P = 0.015) in catatonics (mean 255.75, S.D. +/- 226.54) than in healthy controls (38.6, +/- 27.4) and non-catatonic non-dyskinetic psychiatric patients (57.1, +/- 120.8) whereas there was no significant difference between catatonics and non-catatonic dyskinetic psychiatric patients (453.4, +/- 128.5). There were significantly positive correlations between CPK and AIMS, as well as significantly negative correlations between CPK and SEPS, in all three groups. Our results suggest that increased serum CPK in catatonia may be related to occurrence of dyskinetic movements. Furthermore, we were able to distinguish a parkinsonic (low CPK, low AIMS, high SEPS) and a dyskinetic (high CPK, high AIMS, low SEPS) subtype in catatonia.

[The predisposition to catatonic reactions, monoamine oxidase and the delta-sleep peptide in rats]. / Predraspolozhenie k katatonicheskim reaktsiiam, monoaminoksidaza i peptid del'ta-sna u krys.

MAO B/MAO A rations and the influence of delta-sleep inducing peptide (DSIP) on the two forms of MAO and on the predisposition to different types of catatonic reactions were compared in rats of GC strain selected from Wistar for predisposition to catalepsy, and in wild rats. In GC rats, the MAO B/MAO A ratio was increased, as compared to Wistar, in the brain stem and hemispheres, whereas in wild rats predisposed to catatonia it was increased, as compared to normal wild rats, only in the hemispheres. In GC rats, this increase of the MAO B/MAO A ratio was due to a decrease of MAO A and increase of MAO B activity, while in wild catatonic rats only due to heightened MAO B activity. Administration of DSIP abolished the susceptibility to catatonic reactions and normalized the MAO B/MAO A ratio both in GC and in wild catatonic rats. There seems to be a partial similarity of physiological mechanisms of catatonic reactions in laboratory albino and in wild rats.

Psychogenic catatonia with elevated creatine kinase and autonomic hyperactivity.

A case is presented in which a young man with no psychiatric history and no previous exposure to psychotropic medication rapidly developed severe catatonia and autonomic hyperactivity, and an elevated creatine kinase level. He was treated with electroconvulsive therapy and recovered completely. This case suggests that a subgroup of patients who presented with symptoms resembling those of neuroleptic malignant syndrome and who have been treated with neuroleptics may suffer from severe psychogenic catatonia.

[Multiple forms of monoaminoxidase in the rat brain during experimental catatonia]. / Mnozhestvennye formy monoaminoksidazy golovnogo mozga krysy pri éksperimental'noi katatonii.

Catalytic properties of multiple forms (separated by affinity chromatography) of rats brain mitochondrial monoamine oxidase (MAO, MAO-I, MAO-11 alpha, MAO-11 beta, MAO-111) have been studied in the animals selected for propensity to development of catatonic syndrome considered as an experimental model of the catatonic syndrome occurring in schizophrenia. It was shown that in experimental catatonia (as compared with rats of the corresponding control group) there was a dramatic increase in the brain stem of the rate of oxidative deamination of beta-phenylethylamine catalyzed by MAO-III; there was also a statistically significant (albeit less expressed than in the experiments with beta-phenylethylamine) increase in the rate of deamination of tyramine and a decrease in the rate of deamination of serotonin. In the systems with MAO-II beta we detected statistically significant increase in the rates of deamination of tyramine and beta-phenylethylamine in experimental catatonia as compared with corresponding control. Studies of multiple forms of brain MAO provide more informative data than estimation of "total" MAO activity (without separation of the multiple forms of this enzyme).

'Catatonia' due to disulfiram toxicity.

In an alcoholic patient, catatonia developed while he was receiving disulfiram (Antabuse). Resolution of the question whether his state was classically catatonic required a detailed review of the literature on the subject. The conclusion reached is that the original definition still holds for psychiatric illness, but application of the term to neurological and metabolic states has often been based on imprecise criteria and failure to consider akinetic mutism and extrapyramidal motor disturbances as factors. The action of disulfiram as an inhibitor of dopamine beta hydroxylase provides a possible mechanism for the cerebral toxic effect, but nonetheless the various interpretations remain largely speculative.