Inhibitory cardiovascular function of neurons in the caudal ventrolateral medulla of the rabbit: Relationship to the area containing A1 noradrenergic cells

Experiments were performed to test the hypothesis that A1 noradrenergic neurons, in the caudal ventrolateral medulla, have an inhibitory cardiovascular function. The lateral portion of the caudal medulla was systematically explored, using focal electrical stimulation, in anesthetized, paralyzed rabbits and arterial pressure and heart rate responses were recorded. Since electrical stimulation activates fibers of passage as well as neuronal cell bodies, we also determined cardiovascular responses to microinjections of L-glutamate, a neuroexcitatory amino acid with minimum effects on fibers of passage. Histological studies of stimulation sites were combined with catecholamine fluorescence histochemical studies to localize the A1 cells. A decrease in arterial pressure and heart rate, restricted to the region containing A1 cells, was observed with low frequency stimulation and with microinjections of L-glutamate. In contrast, when GABA, an inhibitory amino acid, was microinjected into the A1 region, we observed an increase in arterial pressure and heart rate. L-Glutamate and GABA responses were dose-related. The fall in pressure was independent of the fall in heart rate. Results support our hypothesis, providing evidence that neurons in the A1 area tonically inhibit sympathetic vasomotor tone.     

Retrograde transport of dopamine β-hydroxylase antibodies in sympathetic neurons: Effects of drugs modifying noradrenergic transmission

Antibodies to dopamine beta-hydroxylase (anti-D beta H) were taken up by noradrenergic nerve terminals in the iris following attachment to D beta H, and were transported back to, and accumulated in, the superior cervical ganglion (SCG). Concurrent, or prior destruction of noradrenergic terminals with 6-hydroxydopamine, injected intraocularly, blocked the retrograde transport of anti-D beta H. However, recovery was rapid, reaching 50% of control values within 1 day. Such transport was characterized by a shorter time period before accumulation could be detected in the SCG and by a slower rate of accumulation. These results suggest that noradrenergic neurons recover their ability to turn over synaptic vesicles by exocytosis and transport these back to the ganglion early during the period of axonal regeneration when the axonal length is shorter than normal. The uptake and transport of anti-D beta H was regulated by alpha-adrenergic agents administered locally in the vicinity of noradrenergic nerve terminals. Thus intraocular injection of phentolamine resulted in an increased accumulation of anti-D beta H in the SCG, while amphetamine and the postsynaptic alpha-receptor antagonist, phenylephrine, decreased accumulation. Clonidine and desipramine, which have a predominant presynaptic action, failed to influence the transport of anti-D beta H. These results suggest that in vivo the uptake of anti-D beta H can be increased more by local postsynaptic reflex actions than by a mechanism depending on the inhibition of presynaptic alpha-receptors.     

Analgesia produced by microinjection ofl-glutamate into the rostral ventromedial bulbar nuclei of the rat and its inhibition by intrathecal α-adrenergic blocking agents

Definite and dose-dependent analgesia followed microinjection ofl-glutamate into the nucleus reticularis paragigantocellularis (NRPG) of rats. This analgesic effect was inhibited by lumbar intrathecal pretreatment with phenoxybenzamine and phentolamine but not by propranolol, methysergide or naloxone. Microinjection ofl-glutamate into the nucleus raphe magnus (NRM) also produced an analgesic effect which was reduced by intrathecal pretreatment with methysergide but not by phentolamine. These findings provide direct evidence that the NRPG and NRM function separately in descending pain-suppression systems of the spinal cord.     

Reaction of the mutant mouse nude to axonal injuries of the central nervous system.

The effects of unilateral forebrain and spinal cord hemisections were examined in the mutant athymic mouse nude. The activities of tyrosine hydroxylase and glutamic acid decarboxylase within the striatum and olfactory tubercle and within the midbrain ventral tegmentum, terminal fields of dopaminergic and GABA-ergic neurons, respectively, were measured to characterize the anterograde reaction of these neurons to axonal injuries. After forebrain hemisections a rapid (within 2 days) and permanent decrease was observed for all enzymes, indicating a permanent degeneration of axons with no recovery. Unilateral spinal cord hemisections resulted in a flaccid paralysis of the ipsilateral hind limb which subsided within 2 to 3 days after the lesion, and thereafter a permanent spasticity ensued. When spinal cord hemisection was repeated the initial flaccid paralysis did not occur and spasticity of the ipsilateral hind limb was immediately evident. The results indicate that regeneration of cut axons or even an improved motor recovery does not occur in the central nervous system of the nude mouse.     

Effects of lesions in the ventral noradrenergic bundle on behavior and response to psychotropic drugs in rats.

Bilateral lesions of the ventral noradrenergic bundle (VB) decreased concentration of noradrenaline within the mesendiencephalon but not in the cortex. Lesioned rats showed increased activity measured in the open field test. Cataloptogenic effects of chlorpromazine and haloperidol were almost completely abolished in VB-lesioned animals. The stereotypy induced by both--amphetamine and apomorphine was, however, unchanged. It is supposed that lesions of the VB lead to increased activity in dopaminergic neurons in the brain.     

The neuropeptide Y antagonist PYX2 decreases lordosis behavior

Neuropeptide Y (NPY) has been localized to noradrenergic neurons and both the noradrenergic system and NPY play a facilitatory role in the control of luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH) release. The present experiments examined whether NPY also plays a role in the control of lordosis. Adult female guinea pigs were ovariectomized (ovx) and implanted with a cannula into the lateral ventricle. In Experiment 1, intracerebroventricular (ICV) administration of the NPY antagonist PYX2 (0, 0.5, 2.0 or 10.0 μg) caused a dose-dependent decrease in lordosis behavior in ovx, estrogen and progesterone-primed guinea pigs. In addition to an effect on the mean lordosis response, PYX2 also decreased the percent of animals showing lordosis and the maximum lordosis response. In Experiment 2, NPY administration (25 μg, ICV) 30 min after PYX2 (2 μg, ICV) to ovx estrogen and progesterone-primed females significantly reversed the effect of the PYX2. Because the NPY antagonist PYX2 reversibly decreased lordosis behavior this suggests that NPY plays a facilitatory role in the control of lordosis behavior.