Release into the cerebral ventricles of substances with possible transmitter function in the caudate nucleus

Abstract

1. One caudate nucleus of the anaesthetized cat was superfused by perfusing the anterior horn of one lateral cerebral ventricle. The perfusates were examined for their content in acetylcholine (ACh), dopamine, homovanillic acid (HVA) and 5-hydroxytryptamine (5-HT), at rest and after a variety of stimuli.2. When prostigmine was added to the perfusion fluid, ACh appeared in the effluent; its concentration tended to rise in the course of an experiment. Various afferent stimuli, all of which caused evoked responses recorded from the contra-lateral caudate nucleus, increased the ACh content of the effluent. Effective stimuli were noise and electrical stimulation of afferent nerves or of certain regions of the brain including the ipsi-lateral substantia nigra.3. The dopamine content of the effluent was extremely low (of the order of 50 pg/min) at rest, but, on occasion, rose sharply when the substantia nigra was stimulated electrically with trains of pulses repeated once every 3 sec. The results were inconsistent.4. Since dopamine in tissue is rapidly transformed enzymically into HVA, the appearance of this acid in the perfusate was examined.5. At rest, HVA was found to appear in the effluent at a rate of 2-8 ng/min. Its concentration was rapidly depressed by increasing the depth of anaesthesia.6. Stimulation of the substantia nigra for periods of 3 or 4 min caused an increment in the HVA content of the effluent lasting 1 hr or more. It was frequently seen when two points of the substantia nigra were stimulated simultaneously, less regularly with only one stimulating electrode, and rarely if this was placed in the most caudal part of the substantia nigra.7. These results strongly support the view that there is a dopaminergic nigro-striatal pathway. The following assumption would explain the erratic appearance of dopamine and the long duration of increments in HVA: many of the axons originating in the substantia nigra end either in the putamen or in parts of the caudate nucleus which are far away from the ventricular surface; any dopamine released from these axons will not reach the ventricular surface at all, and HVA will, at best, reach it very slowly.8. Small amounts of 5-HT appeared in the ventricular perfusate, and the quantity rose after the administration of monoamine oxidase inhibitors. It was not increased by the type of stimuli used in this work to elicit the release of ACh or HVA.