[The inhibition of action. Interdisciplinary approach of its mechanisms and physiopathology]. / L'inhibition de l'action. Approche interdisciplinaire de ses mécanismes et physiopathologie.

The author recalls his group's work during the three past decades and how, starting from the study of traumatic states, he established the distinction between shock and stress, physiologically and biologically speaking. According to him, stress supposes a memory process, i.e. the learning of the inefficiency of action in controlling the environmental characteristics. This learning involves cerebral areas and nerve tracks which, as behavioural consequences produce action inhibition. In the neurophysiological field, he underlines the importance, for these mechanisms, of the cortex, dorsal Ammon's horn, lateral tonsil and subthalamic nucleus. He shows why it seems obvious that the mediators of the action inhibiting system are acetylcholine and serotonin. He also recalls the many experimental facts which allow to say that the action inhibiting system is responsible for the release of the hypothalamic-hypophyseal-adrenocortical reaction and of the peripheric sympathetic adrenergic reaction to aggression. He finally shows the function of these two systems where the main pathological accidents originate. He also stresses the discovery and the introduction in the therapeutical paraphernalia of a new molecule minaprine, which he considers as inhibiting action inhibition, and as such, as an indirect anti-depressive drug. The pathology, which is said psychosomatic, thus becomes a pathology of action inhibition, where unconscious memory of past interdictions and failures, relates the subject and his present reaction to environment, to his whole psycho-social past.

Platelet-induced neurogenic coronary contractions due to accumulation of the false neurotransmitter, 5-hydroxytryptamine.

The purpose of this study was to determine if 5-hydroxytryptamine released from aggregating platelets could be accumulated and released by canine coronary adrenergic nerves, and if the false neurotransmitter resulted in an abnormal response of the smooth muscle to nerve stimulation. Isometric tension was measured in rings of epicardial coronary suspended in organ chambers filled with physiological salt solution. The response to electrical stimulation or exogenously added norepinephrine was elicited after contraction with prostaglandin F2 alpha. Electrical stimulation and exogenous norepinephrine caused beta-adrenergic relaxation of control rings. However, after rings were exposed for 2 h to aggregating platelets or 5-hydroxytryptamine, electrical stimulation caused frequency-dependent contractions. These contractions were prevented by the serotonergic antagonists, cyproheptadine or ketanserin, or by the neuronal uptake inhibitor, cocaine. The relaxation caused by exogenously added norepinephrine was unchanged after exposure to platelets or 5-hydroxytryptamine, indicating that smooth muscle alpha- and beta-adrenergic responsiveness was unchanged. The electrically stimulated overflow of radiolabeled norepinephrine from superfused strips of coronary artery was not altered by prior exposure to 5-hydroxytryptamine, indicating that the effect of exposure on the response to electrical stimulation is primarily at smooth muscle serotonergic receptors. Canine coronary arteries accumulated and metabolized radiolabeled 5-hydroxytryptamine in vitro. The accumulation of 5-hydroxytryptamine was inhibited by cocaine or by adrenergic denervation with 6-hydroxydopamine but unaffected by removal of endothelium, indicating that the adrenergic nerves were the primary site of accumulation. Electrical stimulation of superfused strips of coronary artery preincubated with radiolabeled 5-hydroxytryptamine caused the release of the intact indoleamine; this was blocked by the neurotoxin, tetrodotoxin. These studies suggest that 5-hydroxytryptamine liberated from aggregating platelets may be accumulated by coronary adrenergic nerve endings. Upon its release from the nerves as a false transmitter, the amine can activate serotonergic receptors on the smooth muscle and reverse the action of the adrenergic nerves from dilator to constrictor.