Low brain serotonin transporter binding in major depressive disorder.
123I-ADAM SPET imaging of serotonin transporter in patients with epilepsy and comorbid depression.
Serotoninergic and non-serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat.
(19/28)Experiments were conducted on anaesthetized, paralysed and artificially ventilated cats in order to determine if the altered discharge pattern of phrenic motoneurones recorded during stimulation of medullary raphe nuclei (raphe magnus (r. magnus), raphe obscurus (r. obscurus), raphe pallidus (r. pallidus] are related to release of serotonin (5-hydroxytryptamine, 5-HT) at synapses on respiratory neurones. Effects of 5-HT released by the neurotoxin p-chloroamphetamine (PCA) on spontaneous activity of phrenic motoneurones were also examined. In addition, responses of phrenic motoneurones to 5-HT applied by micro-electrophoresis were recorded. Stimulation (100 Hz) of r. magnus or r. obscurus depressed the spontaneous inspiratory discharges of phrenic motoneurones. Administration of the 5-HT receptor antagonists cinanserin, methysergide or methergoline reduced, but did not abolish, the inhibition. Inhibition of the neuronal reuptake of 5-HT with fluoxetine enhanced the inhibition and reduced the peak inspiratory action potential frequency of spontaneous discharges. Stimulation (100 Hz) of r. pallidus produced increased firing of phrenic motoneurones. Firing of phrenic motoneurones was evoked even during the normally quiescent expiratory phase of spontaneous respiratory activity. Antagonists at 5-HT receptors reduced the degree of tonic firing, resulting in partial restoration of expiratory pauses during r. pallidus stimulation. Inhibition of 5-HT reuptake, on the other hand, resulted in increased tonic firing. Release of 5-HT by PCA produced a rapid and severe reduction of phrenic nerve activity. Activity was restored by 5-HT receptor antagonists. In reserpine-treated cats, effects of stimulating medullary raphe nuclei were still pronounced, however 5-HT receptor antagonists had no effect on the responses. These results, along with the observation that 5-HT receptor antagonists are only partially effective in non-reserpinized cats, indicate that non-serotoninergic influences contribute as well to the responses evoked by raphe stimulation. Micro-electrophoretic application of 5-HT by large ejecting currents (100-200 nA) had weak stimulatory effects on twenty of forty-five phrenic motoneurones, which exhibited small increases in peak inspiratory discharge frequency during 5-HT application. Ejecting currents less than 100 nA were without effect. It is concluded that 5-HT analogues and agents which release endogenous 5-HT after parenteral administration do not act directly at synapses on the soma membranes of phrenic motoneurones.(ABSTRACT TRUNCATED AT 400 WORDS) (+info)
Involvement of serotonin in the excitation of phrenic motoneurons evoked by stimulation of the raphe obscurus.
(20/28)Short-latency averaged responses in the C5 phrenic nerves to electrical stimulation (2.5-80 microA; 5-80 Hz; 150 microseconds pulse duration) of raphe pallidus (RP) and raphe obscurus (RO) were investigated in anesthetized, paralyzed, and artificially ventilated cats. The responses to stimulation of RO were excitatory, whereas a mixture of inhibitory and excitatory responses of lesser magnitude were observed after stimulating in RP. The maximal response was obtained from the ventral part of RO and consisted of early and delayed excitatory responses that were of equal magnitude in both left and right C5 phrenic nerve roots. The mean latency for the early response was 2.5 +/- 0.1 msec and for the delayed response was 7.0 +/- 0.2 msec. Both responses were elicited during inspiratory phase stimulation, but only the delayed response was present during expiratory phase stimulation. The stimulus threshold of the early response was 5 microA; the delayed response was elicited at currents as small as 2.5 microA. Early and delayed responses were affected in different ways by increasing stimulus current and by increasing stimulus frequency. Intravenous administration of serotonin receptor antagonists methysergide (0.1-0.7 mg/kg), metergoline (33-244 micrograms/kg), and cinanserin (1.5-9.0 micrograms/kg) caused significant dose-related reductions in the magnitude of the delayed response, but did not significantly affect the early response. These data suggest that the early and delayed excitatory responses are mediated by different neuronal pathways. The early response does not involve serotonin release, while the later response is mediated at least in part by activation of a serotonergic pathway.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
Serotonin depolarizes type A and C primary afferents: an intracellular study in bullfrog dorsal root ganglion.
(21/28)Intracellular recordings were obtained from the somata of type A and C primary afferents in the isolated bullfrog dorsal root ganglion (DRG) preparation. Bath application of serotonin (5-HT) in concentrations of 0.25-1.0 mM led to slow and fast depolarizing responses. Slow, maintained 5-HT depolarizations were observed in 47% of type A and 70% of type C neurons. These slow depolarizations were associated with an underlying increase in input resistance (Rin). In some type A neurons, the Rin increase was masked by a decrease in Rin due to depolarization-induced rectification. The slow 5-HT depolarization of type A, but not type C neurons showed pronounced tachyphylaxis to repeated 5-HT applications. In type C afferents, serotonin's slow action was often accompanied by spontaneous firing. Manganese decreased slow 5-HT depolarizations of both cell types. A slow depolarization and excitation of type C afferents by methysergide and cinanserin was also observed. Fast transient 5-HT depolarizations accompanied by a rapid decrease in Rin were observed in 7% of type A and 24% of type C neurons. In some DRG cells the fast and slow depolarizations combined to form a biphasic response. The actions of 5-HT reported here resemble in some ways 5-HT responses recorded extracellularly from the spinal terminations of primary afferents. (+info)
Specificity of serotoninergic inhibition in Limulus lateral eye.
(22/28)The receptor specificity for synaptically mediated lateral inhibition in Limulus lateral eye retina was studied by structure-activity correlations of the action of the putative indoleaminergic neurotransmitter, serotonin (5-HT), and its isomers and structural analogs, tryptamine (TRYP), 6-hydroxytryptamine (6HT), 5,6-dihydroxytryptamine (5,6-DHT), 5-hydroxydimethyltryptamine (5-HDMT), and 5-hydroxytryptophan (5-HTP). The 5-HT blockers, lysergic acid diethylamide (LSD), bromo-LSD (BOL), and cinanserin, were also tested. The inhibitory action of the indoleaminergic agonists is highly structure-specific. An hydroxyl group in the 5 position of the indole nucleus, sterically unencumbered by hydroxyls in neighboing positions, is essential. In order of decreasing potency, 5-HT, 5-HDMT, and 5-HTP are active agonists; TRYP, 6-HT, and 5,6-DHT are inactive. Configuration and mobility of the side chains of the active agonists also affect the interaction, and these side-chain characteristics correlate with agonist potency. The receptors for inhibitory action and for transmembranal transport in reuptake are different. Both active agonists and inactive analogs appear to be taken up (Adolph and Ehinger, 1975. Cell Tissue Res. 163:1-14). LSD and BOL have bimodal actions: direct inhibition and agonist blockade. These actions may be mediated via low-specificity presynaptic uptake receptor sites rather than highly specific, postsynaptic, agonist receptor sites. (+info)
The modification of lumbar motoneurone excitability by stimulation of a putative 5-hydroxytryptamine pathway.
(23/28)1 Changes in lumbar motoneurone excitability were monitored by recording spinal reflex activity from the ventral roots of rats anaesthetized with fluothane.2 Electrical stimulation of nucleus raphes medianus increased the amplitude of the monosynaptic reflex via a pathway having a slow conduction velocity. Stimulation elsewhere in the lower brain stem was less effective. This increase in motoneurone excitability was potentiated by the intravenous injection of L-tryptophan and reduced by intravenous injections of lysergic acid diethylamide (LSD), methysergide or Cinanserin.3 Extracellular field potential responses to stimulation of dorsal or ventral roots were recorded with six barrelled microiontophoresis electrodes. Stimulation of nucleus raphes medianus and iontophoretic application of 5-hydroxytryptamine (5-HT) both increased the excitability of lumbar motoneurones as reflected by an increase in field potential amplitude.4 Responses to both stimulation of raphe nuclei and iontophoretic application of 5-HT were reduced by iontophoretic application of Cinanserin and methysergide.5 The similarities of the responses of lumbar motoneurones to applied 5-HT and activity within the raphe-spinal pathway are discussed. It is suggested that activity within the raphe-spinal pathway can increase lumbar motoneurone excitability via the release of 5-HT in the ventral horn of the spinal cord. (+info)
Regional differences in the response to vasoconstrictor agents of dog and monkey isolated coronary arteries.
(24/28)Contractile responses to vasoconstrictor agents were compared in helical strips of dog and monkey epicardial coronary arteries of different sizes. Contractions of large, medium and small arteries induced by KCl ( 30mM ) were virtually identical. Contractions induced by 5-hydroxytryptamine (5-HT) (10(-9) - 2 X 10(-6) M) were in the order of large greater than medium greater than small arteries in dogs, and large = medium greater than small arteries in monkeys. Cinanserin suppressed these responses. In contrast, contractions produced by angiotensin II (AII) (10(-7) M) were in the order of small greater than medium greater than large arteries in dogs, and small greater than medium = large arteries in monkeys. Sar1-Ala8-angiotensin II markedly attenuated the peptide-induced contractions. Contractions induced by prostaglandin F2 alpha (PGF2 alpha) were significantly greater in large and medium sized arteries than in small arteries in dogs, while those of the arteries of different sizes isolated from monkeys did not differ. Contractions induced by carbocyclic thromboxane A2 (c-TXA2), in arteries of different sizes in dogs and monkeys, did not differ. These results suggest that the sensitivity and/or the population of 5-HT receptors are greater in proximal coronary arteries than in distal arteries, while, in contrast, the sensitivity and/or population of AII receptors are greater in distal coronary arteries. Receptors for PGF2 alpha and c-TXA2 appear to react to a similar degree in monkey arteries of different sizes, although receptors for PGF2 alpha appear to be fewer in distal coronary arteries in dogs. (+info)