Local Treatments of Dorsal Raphe Nucleus Induce Changes in Serotonergic Activity in Rat Major Cerebral Arteries

Abstract

Background and Purpose-Rat major cerebral arteries seem to receive serotonergic fibers originating from the dorsal raphe nucleus (DRN), but little is known about their function. The aim of our present work was to establish a functional relationship between this brain stem nucleus and the cerebral blood vessels by studying the effects of several treatments in the DRN on cerebrovascular serotonergic activity. Methods-Serotonin, clomipramine, 8-OH-DPAT, and WAY-100635 were administered in DRN. A stereotaxically localized electrode allowed the electrical stimulation of this brain stem nucleus. Serotonergic activity was appraised in major cerebral arteries, striatum, and hippocampus from 5-hydroxytryptophan accumulation after aromatic L-amino acid decarboxylase inhibition with NSD-1015. Results-Serotonin significantly decreased serotonergic activity in major cerebral arteries and striatum without affecting it in hippocampus. This reduction was blocked by previous injection of WAY-100635 in DRN. Local administration of 8-OH-DPAT or clomipramine elicited an effect similar to that of serotonin, whereas that of WAY-100635 did not modify serotonergic activity in either of the tissues. Electrical stimulation of DRN significantly increased serotonergic activity in major cerebral arteries and striatum but not in hippocampus. Conclusions-These results confirm the presence of a serotonergic innervation in rat major cerebral arteries functionally related to DRN. 5-HT 1A receptor activation partly mediates the action of serotonin in DRN. A serotonergic tone acting on these somatodendritic receptors was not clearly found. (Stroke. 1999;30:1695-1701.)

Spontaneous Oscillations in Cerebral Blood Flow Velocity Give Evidence of Different Autonomic Dysfunctions in Various Types of Headache

“…These fibers were of central origin, because the serotonin (5‐HT) levels in rat intraparenchymal microvessels decreased after the DRN and the median raphe nuclei were destroyed, which did not occur after superior cervical sympathectomy. Other experiments support this theory of neuronal discharge from the locus coeruleus and the DRN via axons to the intracranial vessels responsible for changes in vessel diameter with concomitant CBFV changes 10‐12,37 . The bilateral changes in B wave activity in our study also supports the assumption that B waves are generated by brain stem nuclei, as hemispheric autonomic centers show a difference regarding autonomic activity 38 .…”

“…Other experiments support this theory of neuronal discharge from the locus coeruleus and the DRN via axons to the intracranial vessels responsible for changes in vessel di-ameter with concomitant CBFV changes. [10][11][12]37 The bilateral changes in B wave activity in our study also supports the assumption that B waves are generated by brain stem nuclei, as hemispheric autonomic centers show a difference regarding autonomic activity. 38 For example, in the intracarotid amobarbital procedure (ie, the Wada test), the heart rate increases after left hemispheric inactivation but decreases after right hemispheric inactivation.…”

“…However, there is experimental evidence from animal and human studies that these fluctuations in vessel diameter are triggered by monoaminergic and serotonergic centers in the midbrain and pons 7,8 . Neurons from the noradrenergic locus coeruleus and the serotonergic dorsal raphe nuclei (DRN) send axons to the small intracranial vessels and are involved in intracerebral vascular control 9‐12 …”

“…7,8 Neurons from the noradrenergic locus coeruleus and the serotonergic dorsal raphe nuclei (DRN) send axons to the small intracranial vessels and are involved in intracerebral vascular control. [9][10][11][12] Since the observation of Raskin et al in headache-free patients who developed migraine-like episodes after stereotactic creation of lesion in the DRN, a role for the brain stem in the etiology of migraine has been proposed. 13 Recent experimental and clinical data have suggested that migraine involves a temporary aseptic perivascular inflammation in the dura from trigeminal antidromic release of neuropeptides such as calcitonin gene-related peptide (CGRP), substance P, and other tachykinins.…”

Spontaneous Low-Frequency Oscillations in Cerebral Vessels: Applications in Carotid Artery Disease and Ischemic Stroke

“…40 Serotonergic nerves from the brainstem’s median and dorsal raphe nuclei project to major resistance vessels, 41 and electrical stimulation of the dorsal raphe nucleus leads to serotonergic activity in major cerebral arteries. 42 These findings suggest that a central pacemaker may be located in the brain stem.…”