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Aminergic modulation in lobster stomatogastric ganglion. I. Effects on motor pattern and activity of neurons within the pyloric circuit.

We investigated the effects of dopamine, octopamine, and serotonin on the motor output of the pyloric circuit in the stomatogastric ganglion of the lobster, Panulirus interruptus. Amines were bath applied at concentrations from 10(-8) to 10(-4) M, and the responses of the six classes of pyloric neurons were monitored both intracellularly and extracellularly. Each amine modified the pyloric motor pattern in a specific way. In addition, dopamine and octopamine were each able to produce different motor patterns at different concentrations. Amine effects on pyloric neurons included initiation and enhancement or inhibition of spike activity, changes in the phase relationships of neurons, and changes in the cycle frequency of the pyloric rhythm. These results show that the motor pattern produced by this well-studied central pattern generator circuit is highly plastic and can be modulated by endogenous biogenic amines.

Action Potentials↗

Distributed amine modulation of graded chemical transmission in the pyloric network of the lobster stomatogastric ganglion.

1. In the pyloric network of the lobster stomatogastric ganglion, graded synapses organize the network output. The amines dopamine (DA), serotonin, and octopamine each elicit a distinctive motor pattern from a quiescent pyloric network. We have examined the effects of these amines on the graded synaptic strengths between the six major types of neurons of this network to understand how amine modulation of synaptic strength contributes to the amine-induced motor patterns. Here we tested amine affects at 10 different graded chemical synapses of the pyloric network. We show that each amine has a statistically different spectrum of distributed effects across the network synapses. 2. Under our control conditions (isolated pairs of neurons, removal of modulatory input), most of the graded chemical synapses were weak and some synapses were nonfunctional. The output synapses of the ventricular dilator (VD) neuron were significantly stronger than the other synapses. 3. DA altered the synaptic strength of every graded chemical synapse. This amine strengthened the weak chemical output synapses of the anterior burster (AB), lateral pyloric (LP), and pyloric constrictor (PY) neurons and weakened (and in some cases abolished) the strong chemical output synapses of the VD neuron. The AB-->inferior cardiac neuron (IC) and PY-->IC graded chemical synapses were nonfunctional under our control conditions; DA activated these silent synapses. 4. Serotonin enhanced the AB's output chemical synapses but weakened all the other graded chemical synapses examined. Octopamine's effects were much weaker than those of the other two amines. It enhanced the AB-->LP synapse and the LP's output synapses and weakly strengthened the AB-->PY, VD-->LP, and VD-->PY synapses. 5. The amines alter the input resistance of many of the pyloric neurons, and this could contribute to the observed changes in synaptic strength by altering passive current flow between input and output sites in the cells. However, the input resistance changes were relatively small compared with the changes in synaptic strength and cannot alone account for the synaptic modulation. In some cases the sign of the input resistance change was inconsistent with the change in synaptic strength. Thus the amines appear to modify synaptic transmission directly in this system. 6. This study completes our description of amine effects on all the graded synapses of the pyloric network. We summarize our present and earlier work to show that modulators can reconfigure the entire synaptic organization of a neural network by acting at many distributed synaptic sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

Metamodulation of the biogenic amines: second-order modulation by steroid hormones and amine cocktails.

An evolutionarily conserved feature of neural systems is that they can be modified by neuromodulators. These modulatory chemical signals include the biogenic amines, octopamine (OA), serotonin (5-HT) and dopamine (DA). Such modulation effectively broadens the operational range in which specific neural circuits can function adaptively. This report discusses how these amines are themselves modulated; for example, by the steroid hormone 20-hydroxyecdysone (20-E) or by the addition of a second biogenic amine. Such second-order neuromodulation, termed metamodulation, is discussed in the context of two well-studied invertebrate systems: the tobacco hornworm moth Manduca sexta, a model of neurodevelopment and plasticity, and the medicinal leech Hirudo medicinalis, a long-favored preparation used to study neural circuits at the level of identified neurons. A portion of this article reviews our previous research of M. sexta that shows that the 'preadult' rise in 20-E is both necessary and sufficient for the increased levels of octopamine observed in the adult. Such elevated levels likely play an important role in the production and modulation of adult behaviors. The somatic growth of median octopaminergic neurons and the late expression of OA-immunoreactivity by novel lateral neurons are also demonstrated to be dependent on 20-E. New immunocytochemical results of stained dopaminergic neurons in the larval and adult moth brain are provided as well, and the potential influence of 20-E on the developmental expression of this neuromodulator is presented. Turning attention to the leech, data indicate that the actions of OA are dramatically altered when 5-HT is combined with OA in the bath surrounding the isolated nervous system. Although either OA or 5-HT alone induces fictive swimming behavior, a cocktail of these two amines strongly inhibits the generation of swimming. Subsequent removal of such a mixture induces nearly continuous swimming and constitutes the best swim-inducing stimulus encountered to date. To understand better how these nonadditive effects are achieved, new results are discussed that indicate that the leech brain is the target of metamodulation by the two amines. Both the arthropod and annelid systems presented here highlight the multiple levels of metamodulation that can exist in nervous systems, and the diverse ways that a modulator's actions can become altered over short or long time periods.

Animals↗

Effects of catecholamines on calvarial bone resorption in vitro.

Many important diseases in otolaryngology manifest through abnormal bone remodeling or destruction. The mechanisms for such pathological remodeling remain poorly understood. Bone is known to be innervated by norepinephrine-containing sympathetic nerves, and sympathectomy is known to induce bone resorption. The role, however, of norepinephrine as a potential bone-modulatory substance is unknown. Using the calvarial calcium release assay, we conducted the following experiment to evaluate the bone-modulatory activity of norepinephrine, the alpha-agonist octopamine, and the beta-agonist isoproterenol. Each agent was tested at 2 concentrations with and without parathyroid hormone. Norepinephrine was found to have no effect on calcium release. In contrast, octopamine at 10(-8) mol/L exerted a significant stimulatory effect on calcium release, and isoproterenol at 10(-6) mol/L exerted a significant inhibitory effect on parathyroid hormone-induced calcium release. The investigation suggests that a bimodal, concentration-dependent, receptor-specific model for catecholamine-mediated modulation of bone resorption may operate in calvarial bone.

Animals↗

Adipokinetic hormone stimulates neurones in the insect central nervous system.

A simple preparation designed to screen and compare the central action of putative neuroactive agents in the moth Manduca sexta is described. This approach combines microinjections into the central nervous system with myograms recorded from a pair of spontaneously active mesothoracic muscles. Pressure injection of either octopamine or Manduca adipokinetic hormone (M-AKH) into the mesothoracic neuropile increases the monitored motor activity. Under the conditions used, the excitatory effects of M-AKH exceed those of the potent neuromodulator octopamine. This suggests that M-AKH plays a role in the central nervous system in addition to its known metabolic functions and supports recent evidence that neuropeptides in insects can be multifunctional.

Amino Acid Sequence↗

[Central action of beta-phenylethylamine derivatives. (4) Effects on spontaneous motor activity and body temperature of beta phenylethyamine derivatives injected into the brain in reserpine pretreated mice].

Effects on spontaneous motor activity and body temperature of beta-phenylethlamine derivatives injected into the cerebral ventricles in reserpine or reserpine and isocarboxazide pretreated mice were investigated with the following results. 1) Each injection of tyramine (40 mug) and dopamine (40 mug) increased the spontaneous motor activity measured by the photo-cell counters method in reserpinized mice. 2) Each injection of tyramine (40 mug), dopamine (40 mug) and beta-phenylethylamine (40 mug) increased the spontaneous motor activity measured by both the wheel cage and photo-cell counters methods in reserpine and isocarboxazide-pretreated mice, but noradrenaline (20 mug) and isoproterenol (80 mug) did not increase the spontaneous motor activity as determined by both methods. 3) The injection of tyramine (40 and 80 mug), dopamine (10 and 40 mug) and p-octopamine (40 mug) increased the body temperature in reserpine and isocarboxazide pretreated mice. 4) Tyramine, dopamine and p-octopamine caused a marked increase in the body temperature as compared with control injection in reserpine and isocarboxazide-pretreated mice, whereas isoproterenol had no influence on body temperature. Our results suggest that beta-phenylethylamine derivatives have different effects in reserpinized and non-pretreated states.

Animals↗

Monoamine control of the pacemaker kernel and cycle frequency in the lobster pyloric network.

The monoamines dopamine (DA), serotonin (5HT), and octopamine (Oct) can each sculpt a unique motor pattern from the pyloric network in the stomatogastric ganglion (STG) of the spiny lobster Panulirus interruptus. In this paper we investigate the contribution of individual network components in determining the specific amine-induced cycle frequency. We used photoinactivation of identified neurons and pharmacological blockade of synapses to isolate the anterior burster (AB) and pyloric dilator (PD) neurons. Bath application of DA, 5HT, or Oct enhanced cycle frequency in an isolated AB neuron, with DA generating the most rapid oscillations and Oct the slowest. When an AB-PD or AB-2xPD subnetworks were tested, DA often reduced the ongoing cycle frequency, whereas 5HT and Oct both evoked similar accelerations in cycle frequency. However, in the intact pyloric network, both DA and Oct either reduced or did not alter the cycle frequency, whereas 5HT continued to enhance the cycle frequency as before. Our results show that the major target of 5HT in altering the pyloric cycle frequency is the AB neuron, whereas DA's effects on the AB-2xPD subnetwork are critical in understanding its modulation of the cycle frequency. Octopamine's effects on cycle frequency require an understanding of its modulation of the feedback inhibition to the AB-PD group from the lateral pyloric neuron, which constrains the pacemaker group to oscillate more slowly than it would alone. We have thus demonstrated that the relative importance of the different network components in determining the final cycle frequency is not fixed but can vary under different modulatory conditions.

Animals↗

The fight and flight responses of crickets depleted of biogenic amines.

Aggressive and escape behaviors were analysed in crickets (Orthoptera) treated with either reserpine, a nonspecific depleter of biogenic amines, or the synthesis inhibitors alpha-methyltryptophan (AMTP) and alpha-methyl-p-tyrosine (AMT) to specifically deplete serotonin, respectively dopamine and octopamine. Standard immunocytochemical techniques were used to verify depletion from central nervous tissue, and determine the effective dosages. Reserpinized crickets became exceedingly lethargic and had severely depressed escape responses. However, they were still able to express all the major elements of the escalating sequences of stereotype motor performances that typifies normal aggressive behavior in the cricket. AMT and AMTP treatment had opposing influences on escape behavior, being enhanced by serotonin depletion, but depressed by dopamine/octopamine depletion. AMTP-induced serotonin depletion had no influence on aggressive or submissive behaviors. AMT-treated crickets could normally only be brought to fight by coaxing. Though capable of expressing aggressive behavior per se, agonistic encounters between AMT-treated crickets were shorter, and rarely involved actual physical interactions. Hence, although amines seem to have similar actions on escape behavior in insects and crustaceans, the aminergic control of aggression seems to be fundamentally different in these arthropods groups. We conclude that amines are not in principle required for the initiation and operation of the motor circuits underlying aggression in the cricket. However, octopamine and/or dopamine seem necessary for establishing a level of excitability sufficient for aggressive behavior to become overt in response to appropriate natural releasing stimuli.

Adrenergic Uptake Inhibitors↗

Comparative pharmacology of feeding in molluscs.

1. This paper reviews the role of transmitters in identified neurons of gastropod molluscs in generating and modulating fictive feeding. 2. In Lymnaea and Helisoma the 3 phase rhythm is generated by sets of interneurons which use acetylcholine for the N1 (protraction) phase, glutamate for the N2 (rasp) phase interneurons. The N3 interneurons are likely to use several different transmitters, of which one is octopamine. 3. In all the species examined, serotonin (5-HT) is released from giant cerebral cells. Other amines, including dopamine and octopamine, are present in the buccal ganglia and all these amines activate or enhance feeding. 4. Nitric oxide (NO), mostly originating from sensory processes, can also activate fictive feeding, but (at least in Lymnaea) may also be released centrally from buccal (B2) and cerebral neurons (CGC). 5. The central pattern generator for feeding is also modulated by peptides including APGWamide, SCP(B) and FMRFamide. 6. There is increasing evidence that most of these transmitters/modulators act on feeding neurons through second messenger systems--allowing them to act as longer-lasting neuromodulators of the feeding network. 7. Many of the transmitters are used in similar ways by each of the gastropods examined so far, so that their function in the CNS seems to have been conserved through evolution.

Acetylcholine↗

Genetic control of biogenic-amine systems in Drosophila under normal and stress conditions.

The contents of octopamine and its precursors (tyrosine and tyramine) were studied in adults of two lines of Drosophila virilis with contrasting stress responses. It was demonstrated that in individuals responding to stress by a hormonal stress reaction (line 101), the contents of octopamine and tyrosine are lower than in nonresponding flies (line 147). It was found that there is no difference between the lines in the level of tyramine under normal conditions. The dopamine response to stressor was also studied. Genetic analysis of these differences revealed that they are controlled by a single gene and that the gene is not sex-linked. The gene controlling the response was found to be linked to chromosome 6 of D. virilis.

Animals↗

[Adaptive value of genes controlling the level of biogenic amines in Drosophila].

The effects of mutations that change the level of biogenic amines (octopamine and dopamine) on stress-reactivity and fitness of Drosophila imagoes are considered. It has been shown that (1) the biogenic amines represent an important but not triggering factor of the development of stress reaction; (2) under normal conditions, reproduction is regulated by genes that control dopamine metabolic pathways (indirectly via regulation of the juvenile hormone level). Under unfavorable conditions, reproduction is regulated by genes that control octopamine metabolism; (3) heat-stress adaptation depends on expression of genes controlling the background level of dopamine.

Adaptation, Physiological↗

The presence of trace amines in postmortem cerebrospinal fluid in humans.

The postmortem levels of biogenic amines in cerebrospinal fluid may represent a useful tool in defining some pathological conditions; no information is available concerning the occurrence of trace amines in postmortem cerebrospinal fluid. Thus, the occurrence of octopamine, synephrine and tyramine were evaluated by using a HPLC system in 20 postmortem samples of cerebrospinal fluid (obtained from 11 males and 9 females) and their levels were compared with those of 20 living subjects (obtained from 11 males and 9 females). The results show that trace amines dramatically increase in the postmortem cerebrospinal fluid (100, 20, and 4 fold increase for tyramine, octopamine, and synephrine respectively). To our knowledge, our data represent the first time trace amines have been identified in postmortem cerebrospinal fluid and the dramatic increase observed for tyramine has the potential of becoming a new tool in forensic science for better defining the time of death.

Amines↗

[Pathogenesis of hepatic encephalopathy (author's transl)].

This contribution presents data from the literature as well as our own results concerning the mechanisms of hepatic encephalopathy (HE). 1. Blood chemistry: In patients with liver cirrhosis, the plasma levels of ammonia, phenylalanine, tyrosine, phenolic acids, and octopamine correlated with the stages of HE. Methionine and free tryptophan concentrations were increased only in stages 2-4. Further, branched chain amino acids were below the normal range. Experimental findings in animals elucidated some mechanisms of these changes. 2. Effects of administered substances: With ammonia, methionine, methanethiol, tryptophan, phenolic substances, and fatty acids central nervous disturbances were observed. 3. Interactions: Anemia, methanethiol, and fatty acids favored ammonia toxicity. Alkalosis diminished cerebral symptoms. 4. Neurotransmitters: HE was accompanied by an enhanced turnover of serotonin and by increased amounts of false neurotransmitters (like octopamine) in the brain. 5. Oxydative brain metabolism: Disorders of cerebral oxygen and glucose utilization were mainly documented in cases of long term HE with EEG alterations. 6. Structural changes of the brain: Most of them are irreversible.

Alkalosis↗

[Pharmacologic peculiarities of natural and synthetic alpha-adrenomimetics].

The mechanical response of the isolated rat vas deferens to four alpha-adrenomimetic substances has been studied. The four test substances were noradrenaline, octopamine, 2-phenylethylamine and 2-(1-naphthylmethyl)imidazoline (Privin). Examination of the cumulative dose/response curves showed both qualitative and quantitative differences. Octopamine gave an alpha value (intrinsic activity) greater than that of noradrenaline; Privin proved to be a partial agonist but with affinity greater than that of noradrenaline. Various qualitative differences were also observed suggesting a possible explanation based on labilization of the membrane.

Adrenergic alpha-Agonists↗

Modification of substrate-inhibitor affinities of human platelet monoamine oxidase B in vitro.

The rate of benzylamine utilization by monoamine oxidase (MAO)-B from human blood platelets was 2-4 times higher than that for octopamine. Both activities were inhibited 100% by 10(-7) M deprenyl (a specific MAO-B inhibitor) and were not affected by clorgyline (a specific MAO-A inhibitor) or by polyclonal antibodies to MAO-A. The preincubation of platelet MAO-B with purified MAO-A from mitochondrial membranes of human placenta resulted in appearance of excess octopamine activity. This additional activity was not precipitated by antibodies to MAO-A or inhibited by deprenyl but was inhibited by clorgyline. Incubation of the MAO-A preparation from placenta at 45 degrees C for 15 min before its preincubation with MAO-B caused 50% loss of both activities. Protease inhibitors had no effect on the modification of MAO. These data indicate that MAO-A or a factor tightly bound to it can modify MAO-B yielding a form of the enzyme with both MAO-A and MAO-B substrate and inhibitor affinities and MAO-B immunospecificity.

Antibodies↗

Pharmacological characteristics of four giant neurons identified in the cerebral ganglia of an African giant snail (Achatina fulica Férussac).

Two giant neurons, d-RCDN (dorsal-right cerebral distinct neuron) and d-LCDN (dorsal left cerebral distinct neuron), with a diameter of about 100 microns, were found symmetrically on the dorsal surface of the cerebral ganglia of an African giant snail (Achatina fulica Férussac). They showed spontaneous spike discharges at a stable frequency. Two giant neurons, v-RCDN (ventral-right cerebral distinct neuron) and v-LCDN (ventral-left cerebral distinct neuron), (diameter, approx. 150 microns) were identified on the ventral surface of the same ganglia. No spontaneous spike discharges were evident. Both d-RCDN and d-LCDN were equally inhibited by dopamine, octopamine, 5-hydroxytryptamine and histamine. Acetylcholine sometimes showed inhibitory effects, but they were not so stable. No substance having excitatory effects on the neurons was found. Both v-RCDN and v-LCDN were equally excited by octopamine, 5-hydroxytryptamine, GABA and acetylcholine and inhibited by dopamine and beta-hydroxy-L-glutamic acid.

Acetylcholine↗

[Interaction of propranolol and somatostatin with the octopaminergic response of honeybee lipemia in vivo].

The injection of DL-octopamine to emerging adult honey bees (1 nanomol per individual) promptly rises the haemolymph levels of steroids, diacyl and triacylglycerols (over 100% increase occurring after 10 min). Free fatty acids are then increased (by 131%) 45 mn after injections. These responses are completely abolished by 2.5 nanomol propranolol and 0.07 nanomol cyclic somatostatin. Octopamine thus seems to be more strongly involved in the lipemia than in the glycemia regulation, by contrast with noradrenaline which is, apparently, more active on carbohydrates.

Animals↗

[Pharmacological pecularities of natural and synthetic alpha-adrenomimetic substances II].

The comparative examination of noradrenaline, octopamine, Privin and 2-phenylethylamine on the isolated rat vas deferens made under controlled conditions (1) has been extended by introducing more complex experimental conditions. Pretreatment of the animal with reserpine does not change the response to Privin, while the response to the maximal doses of noradrenaline is reduced; the response to octopamine remains unchanged while that of 2-phenyl-ethylamine is abolished.

Animals↗