Serotonin-receptors coupled with an adenylate cyclase in the rat brain: non-identity with 3H-5-HT binding sites.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Adrien.
Explore the source record for details and available documents.
Bilateral electrocoagulation of the locus coeruleus (LC) were performed in 8 cats, in order to study the effects on the heart rate modulation during sleep. In 4 cats the lesions were restricted to the posterior part of LC: they induced a permanent tachycardia in all states, and a reduction of the phasic changes during paradoxical sleep (PS), while the state-linked modulations remained similar to those of controls. In another group of 4 cats, lesions extended rostrally to the anterior LC. They induced a bradycardia evidenced mostly during PS. Phasic changes persisted though the tachycardic component was greatly reduced. The state-linked modulations were opposite to those of controls: increase during transition from slow waves sleep (SWS) to PS and decrease during PS. No recovery trend was observed within the 3 weeks post-lesion experimental period. These data are discussed in relation to the well-known parasympathetic and sympathetic regulations of the heart rate, with special attention to the changes observed during transition from slow waves sleep (SWS) to PS and during the first minute of PS. This period corresponds to a shift in the balance of tonic and phasic influences.
Intraventricular injections of 5,7-DHT (.15 mg/g of brain weight) were performed in kittens aged 5 or 30 days. The neurotoxin induced a significant decrease of 5-HT and NA levels in the forebrain in both age groups, whereas a slight increase of each amine was observed respectively in the raphe and lateral brain stem of the younger group (Fig. 1). Pretreatment with desmethylimipramine (20 mg/kg I.P.) resulted in a protection of the noradrenergic system from the neurotoxin (Fig. 2). From the neurophysiological standpoint, 5,7-DHT induced a major paradoxical sleep (PS) insomnia in the one-month-old group, whereas no alteration of PS was observed in the younger group (Fig. 3). The DMI pre-treatment did not modify these results. The hypothesis of brain stem sprouting is discussed, and it is concluded that the serotoninergic system does not mediate the sleep regulation in the early post-natal period.
In the present study, using neonatal intraventricular injections of 6-hydroxydopamine (6-OHDA) and the fluorescence histochemical method for monoamines, it is observed that an extensive plexus of noradrenaline (NA) fibres develops in the pontine region of the cat brain subsequently to the neonatal destruction of the ascending NA bundles and of the NA innervation in the cerebral cortex by the neurotoxin. This plexus is only partly conserved 10 months after the 6-OHDA treatment. Generally, only a limited number of NA perikarya degenerate in the region of the locus coeruleus, the others (nucleus subcoeruleus senso lato) exhibiting the same strong fluorescence as the new NA fibres. Using the radioautographic method after intraventricular injections of [3H]NA, our work demonstrates also the transient disappearance (at least one month) of the uptake of [3H]NA in the pons, whose NA cell bodies and nerve terminals are no longer labeled in the same number as in control animals. The possibility of again labeling significantly NA perikarya and numerous nerve terminals occurred between 3 and 5 months of age, probably indicating both a re-establishment of normal uptake properties in the preserved NA perikarya and nerve terminals and some maturation of the uptake mechanisms in the abnormal NA fibres of the pons. This last observation is at variance with data from newborn animals showing that the uptake of NA develops in parallel with the accumulation of endogenous NA in catecholamine nerve terminals. The present results, however, do corroborate and complement previous biochemical data obtained in the cat after neonatal injection of 6-OHDA.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Intraventricular 6-OHDA was injected in kittens at different stages of development, and the subsequent sleep polygram was analyzed, in order to determine the role of the catecholaminergic system in the ontogenesis of sleep regulations during the first and the second postnatal months. 6-OHDA, used with or without previous chlorimipramine treatment, led within a 10-day period to drastic reductions of the endogenous monoamines in the forebrain of all age groups. Although the neurotoxicity of 6-OHDA was almost constant among the different age groups, the effects on sleep depended on the age of the animals at the time of the injection. In the 5-week-old injected kittens, 6-OHDA affected PS according to an adult-like pattern. In the 3-week-old kittens, 6-OHDA alone (leading to both catecholamines and serotonin decreases) induced the same PS deficit as in the adult cat. In the 1- and 2-week-old kittens, neither 6-OHDA alone, nor 6-OHDA with previous chlorimipramine treatment, distrubed the sleep regulations. These data are compared to similar experiments performed in the adult cat. They are discussed in terms of sleep control ontogenesis. It is concluded that the catecholaminergic system plays no important role in the mechanisms of sleep regulation in the early postnatal period in the kitten, whereas its regulatory influence on PS is confirmed in the juvenile animal. The functional maturation of the catecholaminergic system in terms of sleep regulation is achieved between the third and the fifth week of postnatal life.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Intraventricular injection of 6-hydroxydopamine does not modify the states of alertness in the Kitten, if it is performed in the first week of postnatal life. At three weeks of age, it induces the same sleep impairments as those observed in the adult Cat. Therefore, in the immediate postnatal period, sleep control is not achieved through the monoaminergic systems.
Electrolytic lesions of the anterior raphe nuclei in the 4-6 day puppy rat were performed stereotaxically. The subsequent development of the sleep parameters in these animals was followed up to the second month of life. No difference could be found between the lesioned and control rats, neither in the qualitative nor in the quantitative characteristics of slow wave sleep (SWS) and paradoxical sleep (PS). However, when performing identical lesions on 3-5 week-old animals, a relative insomnia was obtained, more severe for PS than for SWS. The correlation of the neurophysiological data with the biochemical analysis of monoamines in the forebrain revealed that the serotoninergic (5-HT) system of the anterior raphe in the early lesioned animals was almost totally destroyed, with no recovery up to 9 months of age. Our results indicate that the anterior raphe nuclei are not functional during the first week of age, in regard to sleep control, whereas they do play an important role in sleep regulation after 3 weeks of age. Furthermore, some compensatory mechanisms which develop in the early lesioned animal as a consequence of the lesion, could explain the exhibition of normal sleep ontogenesis. The possible nature of these mechanisms is discussed in light of the monoaminergic theory of sleep control.
Electrolytic raphe lesion was performed in 4-6-day-old rats and the resulting changes of 5HT metabolism within the central nervous system were analyzed up to 9 months later. As soon as the 2nd day following the selective destruction of B7 and B8 nuclei, forebrain 5HT levels were decreased by more than 75%. This reduction persisted for at least 9 months with no sign of recovery. The time course of 5-HIAA decrease was parallel to that of the indoleamine so that the ratio of 5-HIAA over 5-HT levels in the forebrain of lesioned rats was similar to that estimated in controls, whatever their age. This result would suggest that the remaining serotoninergic neurons in the lesioned rats did not develop a compensatory hyperactivity. The raphe lesion induced no change in MAO activity and synaptosomal tryptophan uptake but a pronounce decrease in the Vmax of synaptosomal KHT uptake process in various forebrain areas occurred. The serotonin sensitive adenylate cyclase activity in colliculi homogenate was not altered by the lesion suggesting that this enzyme was probably located in postsynaptic membranes. In addition, this observation would indicate that 5-HT receptors which are linked to this adenylate cyclase did not become supersensitive following the selective degeneration of serotoninergic neurons. Animals without forebrain serotoninergic innervation might be of great interest to analyse the role of serotoninergic neurons in various functions (sleep, analgesia, thermoregulation).
The topographical distribution of serotoninergic terminals in the neostriatum of the rat and the caudate nucleus of the cat was established owing to the combined use of microdissection techniques and biochemical microassays. The density of 5-HT terminals in various areas of both structures was quantified first by measuring 5-HT levels in microdiscs of frozen tissue. Since the high affinity uptake process for 5-HT appeared undamaged in isotonic homogenates of previously frozen (--5 degrees C) tissues, it was possible to confirm the findings obtained with the measurement of 5-HT levels by also determining 5-HT uptake activity in these microdiscs. However, in the rat neostriatum, but not in the cat caudate nucleus, [3H]5-HT even at a very low extracellular concentration (4.4 -x 10(-8) M) was taken up not only by serotoninergic terminals but also to a significant extent by dopaminergic terminals. In presence of benztropine, this second component was suppressed and [3H]5-HT uptake activity could then be considered as a specific marker of serotoninergic terminals also in the neostriatum of the rat. In both species, 5-HT terminals were mainly localized in the ventrocaudal area of the structure. In this area, 5-HT levels were among the highest values found in the brain (17 ng/mg protein). The density of 5-HT terminals decreased progressively from the acudal to the rostral planes of the neostriatum in rats or the caudate nucleus in cats. The poorest area, i.e. the dorsorostral zone, contained about 4 times less 5-HT than the ventrocaudal zone of the structure. Electrolytic lesion of the dorsalis (B7) and centralis superior (B8) raphe nuclei during early life resulted in a large decrease of 5-HT levels (--90%) in various parts of the neostriatum of adult rats. The present findings might be of interest to further analyze the role of serotoninergic neurons in extrapyramidal functions.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Sub-total lesions of the Nucleus Raphe Dorsalis and Centralis Superior have been performed on 4 to 10 day-old puppy rats. The sleep cycles of these animals, studied up to one month of age, were modified neither quantitatively nor qualitatively by the lesions. Slow sleep with cortical synchronisation was normally present at 21 days of age. It is concluded that the sleep of such animals might be under the control of another system than the serotoninergic Raphe nuclei.