Antagonism of dopamine-mediated inhibition in the nigro-striatal pathway: A mode of action of some catatonia-inducing drugs

doi:10.1016/0006-8993(74)90686-6

Brain Research

Volume 80, Issue 2, 15 November 1974, Pages 219-228

https://doi.org/10.1016/0006-8993(74)90686-6 Get rights and content

Abstract

Recordings were made from single neurones in the caudate nucleus of anaesthetised rats. Dopamine (DA) was applied by iontophoresis to these neurones and its effects compared with those of substantia nigra (SN) stimulation. There was a good correlation between the inhibitory effects of SN stimulation and inhibitory actions of DA. Papaverine and bulbocapnine applied iontophoretically or given intravenously blocked the inhibitory effects of SN stimulation and of DA. The results provide evidence supporting the view that dopamine is the transmitter for the nigro-striatal pathway mediating inhibition in the rat. It is suggested that blockade of this pathway is one of the mechanisms by which bulbocapnine and papaverine produce catatonia.

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The previously common occurrence of catatonic schizophrenia and catatonic symptoms among schizophrenic patients has diminished sharply; catatonic symptoms now occur more frequently in association with severe affective disorders or with general medical conditions. Catatonia is generally viewed as a peculiar and puzzling syndrome and attracts limited attention. Yet significant catatonic symptoms tend to be present in close to 10% of patients admitted to psychiatric inpatient facilities. The dynamic significance of catatonia can be recognized by considering the original biologic role of catatonia in schizophrenia as an opposite to the paranoid disorder. Szondi viewed catatonia as an attempt at self-healing of the paranoid psychosis with its threatening total expansion, by extreme constriction of the ego. The previously predominant primary association of catatonia with schizophrenia has been eclipsed as neuroleptics have supplanted the endogenous self-healing attempt of catatonia, preventing the occurrence of catatonic symptoms in schizophrenia. Neuroleptics in fact duplicate or approximate the symptoms of catatonia by producing mental immobilization, hypokinesis (parkinsonism and dystonia), hyperkinesis (akathisia), and pernicious catatonia in the modern guise of the neuroleptic malignant syndrome (NMS). Patients with past or present catatonic symptoms are particularly vulnerable to NMS, and treatment of catatonia requires avoidance of neuroleptics and the use of benzodiazepines or electroconvulsive therapy (ECT). The extreme negativism and constriction of consciousness in catatonia suggest a primary role of the frontal lobes, with secondary involvement of the extrapyramidal system and its movement disorders. In an attempt to integrate clinical, psychologic, neuropharmacologic, and neurochemical findings, a modern dynamic neuropsychiatry must appreciate the major significance of catatonia.
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^*: Present address: Escuela de Bioanalisis, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.

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Antagonism of dopamine-mediated inhibition in the nigro-striatal pathway: A mode of action of some catatonia-inducing drugs

Abstract

Life Sci.

Brain Research

Ascending monoamine neurons to the telencephalon and diencephalon

Acta physiol. scand.

Dopamine and mental function

Anesthesia and the responsiveness of individual neurons of the caudate nucleus of the cat to acetylcholine, norepinephrine and dopamine administered by microelectrophoresis

J. Pharmacol. exp. Ther.

Biochemical research in schizophrenia

Nature (Lond.)

Caudate nucleus neurones: correlation of the effects of substantia nigra stimulation with iontophoretic dopamine

J. Physiol. (Lond.)

La Catatonie Expe´rimentale par la Bulbocapnine

Relations between the structure of certain methoxyphenylethylamine derivatives and the occurrence of a hypokinetic rigid syndrome

Psychopharmacologia (Berl.)

The role of biogenic amines in the extrapyramidal system

Acta physiol. pharmacol. neerl.

Intrastriatal injection of quaternary butyrophenones and oxypertine: neuroleptic effect in rats

Psychopharmacologia (Berl.)

Observations on the cellular localization of dopamine in the caudate nucleus of the rat

Z. Zellforsch.

Studies on the Mode of Action of some Catatonia-inducing Drugs

Actions of papaverine and bulbocapnine on synaptic transmission in the nigro-striatal pathway in the rat

J. Physiol. (Lond.)

Actions of 3,4-dimethoxyphenylethylamine in relation to the effects of catecholamines on brainstem neurones

Brit. J. Pharmacol.

Antagonism of noradrenaline and dopamine inhibition of brainstem neurones by bulbocapnine

J. Physiol. (Lond.)

Separate demonstration of dopaminergic and non-dopaminergic projections of substantia nigra in the rat

Anat. Rec.