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PubMed1983

Changes in responsiveness of the beta-adrenergic and serotonergic pathways of the rabbit corneal epithelium.

Adrenergic agonists stimulate the synthesis of cyclic AMP by incubated rabbit corneas with the following order of potency: isoproterenol greater than epinephrine greater than norepinephrine. These agonists have the same order of potency when displacing the specific, beta-adrenergic radioligand, 3H-dihydroalprenolol, from beta-adrenergic receptors on membranes prepared from corneal epithelium. At another locus, serotonin stimulates cyclic AMP synthesis. Inhibition of stimulation in vitro by lysergic acid diethylamide, methysergide, cyproheptadine, and spiroperidol demonstrates the specificity of this pathway for serotonin. Topical epinephrine causes subsensitivity or decreased responsiveness of the beta-adrenergic pathway. There is loss of approximately half the beta-adrenergic receptors from the cornea and a similar loss of epinephrine-stimulated cyclic AMP synthesis, both of which return to control levels in 96 hrs. There is no change in affinity for catecholamines and no loss of responsiveness to prostaglandin E2 or serotonin. Pretreatment with nialamide or subsequent treatment with additional epinephrine does not cause further loss of responsiveness. Supersensitivity or increased responsiveness of this pathway occurs following superior cervical ganglionectomy. Topical serotonin causes decreased responsiveness of the serotonergic pathway. When potentiated by nialamide, serotonin causes almost complete loss of serotonin-stimulated cyclic AMP synthesis for 24-48 hrs. There is no loss of responsiveness to epinephrine. Increased responsiveness of this pathway does not occur following superior cervical ganglionectomy. The authors conclude that the corneal epithelium has both beta 2-adrenergic and serotonin-2 pathways, and each pathway exhibits altered responsiveness by similar mechanisms. In response to exogenous or endogenous stimulation, the beta-adrenergic responsive cells and the serotonergic responsive cells apparently regulate the total number of pathway-specific receptors on their surfaces. Furthermore, the authors postulate that two populations of beta-adrenergic responsive cells exist; those on the apical surface of the epithelium that respond to catecholamine in the tears and those near the basal surface that respond to neuronal catecholamine.

Adrenergic beta-Agonists↗

PubMed1996

Neuropharmacological studies on Fusarium toxins-III: Neurochemical investigations on total toxin extracts from F. moniliforme and F. oxysporum.

Neurochemical effects of different fusarial toxins elaborated from F. moniliforme (FM) and F. oxysporum (FO) were investigated. FM showed significant nonspecific and irreversible monoamine oxidase (MAO) inhibition which was qualitatively comparable to that induced by nialamide, a nonselective MAO inhibitor. FO did not exhibit any significant MAO inhibitory effect. FM produced a dose related increase in monoamine concentrations (dopamine, noradrenaline and 5-hydroxytryptamine) in different rat brain areas namely, diencephalon-midbrain, caudate nucleus and pons-medulla. FO, on the contrary, produced marked increase in dopamine concentration in the caudate nucleus with concomitant reduction in noradrenaline levels in diencephalon-midbrain and pons-medulla with little effect on 5-HT concentration. The neurochemical effects of FM and FO are consonant with the earlier reports on the neuropharmacological profile of these toxins. Thus, FM was reported to have nialamide like activity, whereas FO actions were dopaminergic in nature.

Animals↗

PubMed1988

Localization of serotonin-like immunoreactivity in the eyestalk of the prawn Palaemon serratus (Crustacea, Decapoda, Natantia).

A serotonin-like substance in the organ of Bellonci in the eyestalks of embryos, larvae, and adults of the prawn Palaemon serratus was visualized by the use of two specific antisera against serotonin (5-hydroxytryptamine; 5-HT) in combination with peroxidase-antiperoxidase (PAP). The organ of Bellonci, characterized by compact onion bodies distally and degenerating onion bodies proximally, was the only site of the serotonin-like substance in adults, as well as during development in embryos and larvae. Variations in the content of the 5-HT analogue in the adult were detected during the molting cycle. There was more immunoreactivity in specimens fixed at night than in those fixed in daytime. Likewise, colchicine and nialamide injections enhanced the immunoreactivity of the serotonin-like substance. Extirpations of the medulla externa X organ (MEX), a neurosecretory cell group of the optic ganglion medulla externa, produced the same effect.

Animals↗

PubMed1993

Effects of two substituted hydrazine monoamine oxidase (MAO) inhibitors on neurotransmitter amines, gamma-aminobutyric acid, and alanine in rat brain.

Time- and dose-response analyses were undertaken to investigate the effects of the substituted hydrazine monoamine oxidase (MAO) inhibitors iproniazid and nialamide on the following: MAO-A and -B activity; levels of gamma-aminobutyric acid (GABA), alanine (ALA), and the neurotransmitter amines dopamine, noradrenaline, and 5-hydroxytryptamine (serotonin) and their acid metabolites; and the activity of GABA-transaminase and ALA-transaminase. The results showed that these drugs are relatively potent MAO inhibitors but, unlike the unsubstituted hydrazine MAO inhibitor phenelzine, they do not produce increased GABA and ALA levels in brain. These experiments suggest that a free hydrazine group is necessary for MAO inhibitors to also have marked effects on GABA and ALA.

Alanine↗

PubMed1984

The hypothalamo-hypophysial system of the wild carp, Cyprinus carpio L. I. Structure and ultrastructure of the posterior neurohypophysis.

The posterior neurohypophysis (PNH)-pars intermedia complex of the wild and pond carp, Cyprinus carpio L., has been studied by light, fluorescence and electron microscopy. "Gomori-positive" neurosecretory fibres are abundant in the main trunk of the neurohypophysis as well as its roots penetrating the pars intermedia. Terminals of these fibres are in contact with capillaries of the general circulation and with glandular cells of the pars intermedia. Monoaminergic fibres with a weak green fluorescence, somewhat increasing after injection of nialamide into the pond carp, have largely the same distribution. Three types of neurosecretory fibres and their terminals have been recognized in the PNH-pars intermedia complex. Types-A1 and -A2 fibres, containing granules of 140-180 nm and 100-160 nm in diameter respectively, are peptidergic "Gomori-positive". Type-A2 fibres predominate in the PNH. The least frequent monoaminergic type-B fibres have granules of 60-100 nm in diameter. Numerous peptidergic and few monoaminergic neurosecretory terminals make contact with the capillaries located within the roots of the PNH as well as at the border between them and the pars intermedia. Both peptidergic and monoaminergic terminals make direct synaptoid contacts with the gland cells or end close to connective tissue septa, basal lamina or pituicytes. The PAS-positive gland cells and to a lesser degree the lead-haematoxylin-positive gland cells show these relationships with neurosecretory terminals. The question concerning the mode of interaction between peptidergic and monoaminergic structures in the dual control of the gland cells of the pars intermedia of teleosts is discussed.

Animals↗

PubMed1992

Low-threshold, short-latency cutaneous reflexes during fictive locomotion in the "semi-chronic" spinal cat.

Low-threshold, short-latency cutaneous reflexes evoked in ipsilateral hindlimb motor nerves were examined during fictive locomotion. Locomotion in 11 anaemically decerebrated spinal animals (1-3 weeks after transection at T13-L1) was induced by administration of clonidine, L-dopa and nialamide; by administration of the latter two drugs only; or by exteroceptive stimulation in the absence of any drugs. The caudal and lateral cutaneous sural, caudal cutaneous femoral, saphenous and superficial peroneal nerves were stimulated at low threshold (1.5-3 T). Pooled results from all combinations of cutaneous nerves stimulated and muscle nerves recorded show that the initial response was excitatory in 40 of 50 triceps surae and 17 of 20 semitendinosus (St) electroneurograms (ENGs). These excitatory responses occurred at latencies that ranged from 5 to 15 ms and tended to be maximal during the motor nerve's active period in the step cycle (i.e. they were modulated in a phase-dependent manner). Only three inhibitory responses (9-12 ms earliest latency) were encountered in total: in two St ENGs of one animal and in one lateral gastrocnemius-soleus ENG of a different animal. In two animals a "second" excitatory response (15-25 ms latency) was sometimes recorded in triceps surae and St nerves and, interestingly, could be modulated out of phase with the early response. Weak short-latency excitatory reflexes were also found in contralateral St ENGs when examined. Finally, among medial gastrocnemius, lateral gastrocnemius and soleus nerves, excitatory responses due to stimulation of any particular cutaneous nerve tended to be modulated similarly but were of consistently different amplitude among the three. This finding, together with the general observation that excitatory reflexes produced by stimulation of a particular cutaneous nerve were modulated similarly in extensors (or flexors) of different animals, suggests that spinal circuits generating locomotion may indeed exert a stereotypic control over interneurons in specific cutaneous reflex pathways to motoneurons. The results are primarily discussed in terms of the existing evidence for short-latency excitatory cutaneous reflexes in extensors in a variety of locomotive and non-locomotive preparations.

Animals↗

PubMed1994

Voltage-dependent excitation of motoneurones from spinal locomotor centres in the cat.

Lumbar motoneurones were recorded intracellularly during fictive locomotion induced by stimulation of the mesencephalic locomotor region in decerebrate cats. After blocking the action potentials using intracellular QX-314, and by using a discontinuous current clamp, it is shown that the excitatory component of the locomotor drive potentials behaves in a voltage-dependent manner, such that its amplitude increases with depolarisation. As the input to motoneurones during locomotion is comprised of alternating excitation and inhibition, it was desirable to examine the excitatory input in relative isolation. This was accomplished in spinalised decerebrate cats treated with nialamide and L-dihydroxy-phenylalanine (L-DOPA) by studying the excitatory post-synaptic potentials (EPSPs) evoked from the "flexor reflex afferents" (FRA) and extensor Ib afferents, both of which are likely to be mediated via the locomotor network. As expected, these EPSPs also demonstrate a voltage-dependent increase in amplitude. In addition, the input to motoneurones from the network for scratching, which is thought to share interneurones with the locomotor network, also results in voltage-dependent excitation. The possible underlying mechanisms of NMDA-mediated excitation and plateau potentials are discussed: both may contribute to the observed effect. It is suggested that this nonlinear increase in excitation contributes to the mechanisms involved in the production of the high rates of repetitive firing of motoneurones typically seen during locomotion, thus ensuring appropriate muscle contraction.

Action Potentials↗

PubMed1980

Pools of serotonin in the pineal gland of the mouse: the mammalian pinealocyte as a component of the diffuse neuroendocrine system.

In the pineal gland of the mouse the distribution of serotonin (5-HT) and its eventual relationships to a protein secretion were examined by means of fluorescence histochemical (Falck-Hillarp) and ultracytochemical (chromaffin and argentaffin) methods. (1) Yellow formaldehyde-induced fluorophores, characteristic of high concentrations of 5-HT, were found in pinealocytes, interstitial cells and sympathetic adrenergic nerve endings. The 5-HT content was studied according to the circadian variations and different drug treatments. (2) By use of ultracytochemical methods in untreated control mice precipitates indicative of 5-HT were found over dense-core vesicles (DCV; mean diameter: 100 nm) of the pinealocytes and the vesicular compartment of the sympathetic nerve fibers. After reserpine and p-CPA treatments, the reactivity of the DCV disappeared, but the protein secretion accumulated within the DCV was still present. After nialamide treatment the precipitates in the DCV increased and, similar to control mice, masked the protein secretion. Taking into account the specificity and sensitivity of these three complementary methods, previous biochemical data in mammals and ultracytochemical data in submammalian vertebrates, synthesis, storage, catabolism and release of 5-HT in the mouse and hamster pineals are discussed at the cellular level. Different pools of 5-HT are present: agranular and granular in pinealocytes and sympathetic nerve endings; agranular in interstitial cells. In the mouse, only a small portion of the total 5-HT content appears to bae secondarily taken up by the DCV. Within the DCV, 5-HT is possibly bound to a protein secretion of unknown significance (peptidergic neurohormone?). In the pinealocytes, which are sensitive to a large variety of inputs, processes of indole and protein secretion are found. These cells apparently are the recepto-secretory elements of the mammalian pineal gland. They can thus be classified as a member of the diffuse neuroendocrine system of the paraneuron group.

Adrenergic Fibers↗

PubMed1986

Evidence for direct reciprocal interactions between the central rhythm generators for spinal "respiratory" and locomotor activities in the rabbit.

Rhythm generators for locomotion and respiration have been previously identified in the high spinal rabbit treated with nialamide and DOPA. In curarized preparations, with no sensory feedback, simultaneous recordings of motor commands from the nerves to the diaphragm and to several hindlimb nerves have demonstrated that central (intraspinal) interactions exist between these respiratory and locomotor activities. The purpose of the present study was to investigate the nature of these interactions. Two main possibilities existed: "direct" interactions taking place between the rhythm generators; the activity of one of the rhythm generators modifying the other generator's activity at its "output" (at the interneuronal or motoneuronal level). The present analysis of the timing (and resetting) of activities in the phrenic, hindlimb extensor (gastrocnemius medialis) and flexor (tibialis anterior) nerves suggests a strong direct interaction between the two sets of rhythm generators. Each new locomotor cycle thus only begins at the termination of a "long-lasting phrenic burst" and a respiratory burst can only occur at certain parts of a locomotor cycle.

Afferent Pathways↗

PubMed1984

Behavioural effects mediated by unilateral nigral dopamine receptor stimulation in the rat.

Unilateral intranigral injections of dopamine in conscious rats pretreated with nialamide resulted in either ipsiversive or contraversive rotation depending upon the site of injection. Injection of dopamine (50 micrograms) into the zona compacta of the substantia nigra induced weak ipsiversive or mixed ipsiversive and contraversive rotation. Injection of dopamine (12.5-50.0 micrograms) into zona reticulata of substantia nigra induced only contraversive circling. Destruction of the ipsilateral medial forebrain bundle (MFB) using 6-hydroxydopamine (6-OHDA) abolished ipsiversive circling but enhanced contraversive circling produced by dopamine or apomorphine. The combination of a unilateral 6-OHDA lesion of MFB with a kainic acid or electrolesion of the ipsilateral strio-nigral and pallido-nigral pathways reduced contraversive circling to intranigral apomorphine (10 micrograms). Ipsiversive circling produced following intranigral injection of dopamine is dependent upon the integrity of ascending dopamine neurones. Contraversive rotation is independent of ascending dopamine pathways but is reliant upon afferent input to the substantia nigra from the striatum and/or globus pallidus.

Animals↗

PubMed1983

Serotonin distribution in the circumventricular organs of the rat. An immunohistochemical study.

Serotonin-immunoreactive structures in the circumventricular organs (organum vasculosum laminae terminalis, subfornical organ, subcommisural organ and area postrema) of the rat were demonstrated using a modified peroxidase-antiperoxidase immunohistochemical method. Various densities of serotonin fibers were demonstrated in all four circumventricular organs; however, serotonin-positive cells were evident in the area postrema only after nialamide treatment. Serotonergic supraependymal fibers were observed on the surface of the organum vasculosum laminae terminalis and that of the subfornical organ, but not on the subcommissural organ and area postrema. The organ, but not on the subcommissural organ and area postrema. The serotonergic plexus of the basal portion of the subcommisural organ was considered to be continuous with the supraependymal plexus.

Animals↗

PubMed1980

Autoradiographic observations on the distribution and metabolism of N'-/14C/nitrosonornicotine in mice.

The fate of the weak base N'-nitrosonornicotine (2'-14C-labeled) has been studied in mice. Whole-body autoradiography showed that the radioactivity was rapidly distributed throughout the body, which probably reflects an ability of the non-protonated compound to freely pass biological membranes and distribute evenly in the intra- and extracellular tissue water. Metabolites which were firmly bound to tissue macromolecules - retained throughout the observational period (24 h) - were present in the tracheobronchial and nasal mucosa, the liver, the submaxillary and sublingual salivary glands and the esophagus. Radioactivity in the lacrimal gland, the gastrointestinal contents, the urinary bladder, and gallbladder seems to be related to excretion of the substance and/or its metabolites. A binding to the melanin in the eye and hair was observed in vivo and in vitro. Experiments with mice pretreated with diethyldithiocarbamate and nialamide showed that these substances partially inhibited the metabolism of N'-/14C/nitrosonornicotine. CO2 was not recovered in the breath during the 4 h following the administration of N'-/14C/nitrosonornicotine.

Animals↗

PubMed1975

Modifications by lithium of behavioral responses to methamphetamine and tetrabenazine.

Different groups of mice were injected s.c. daily with lithium chloride in three doses(0.52, 1.58 and 4.72meg/kg) or with saline for a period of 3 weeks. Lithium administered acutely or chronically did not affect spontaneous locomotor activities. However, methamphetamine-induced hyper-locomotor activities were inhibited in the lithium groups as compared with those in the saline group, while the hyper-locomotor activities induced by tetrabenazine in the nialamide-pretreated animals were reduced to some extent but not significantly by lithium. Tetrabenazine brought about an initial transient increase followed by a decrease of spontaneous locomotor activities in the lithium groups, whereas it induced only a decrease of the activities in the saline group. In addition, jumping and vertical jumping behaviors, which were not observed in the saline group, occurred 30-60 min after tetrabenazine in the lithium groups. These effects of lithium tended to increase with an increase of the doses administered and with a prolongation of its daily administration. The results demonstrate that lithium modifies behavioral responses to methamphetamine and tetrabenazine.

Animals↗

PubMed1978

Anticonvulsant action of cannabis in the rat: role of brain monoamines.

The role of brain monoamines in the anticonvulsant action of Cannabis indica resin (CI), against maximal electroshock-induced seizures in albino rats, was investigated by using pharmacologic agents that influence brain monoamine activity. Delta-9-tetrahydrocannabinol content of cannabis resin was estimated to be 17%. The anticonvulsant action of CI (200 mg/kg, i.p.) was significantly inhibited after pretreatment with drugs that reduce brain serotonin activity but not by drugs that reduce brain catecholamine activity. Similarly, the anticonvulsant action of a subanticonvulsant dose (50 mg/kg, i.p.) of CI was potentiated by serotonin precursors but not by catecholamine precursors. Potentiation of the anticonvulsant action of CI by nialamide or by imipramine was inhibited after pretreatment with 5,6-dihydroxytryptamine. The results suggest that the anticonvulsant action of CI in the rat is serotonin- and not catecholamine-mediated.

Animals↗

PubMed1979

The central action of pizotifen.

The central action of the potential antidepressant drug pizotifen (Sandomigran) was studied in mice, rats and rabbits. Pizotifen in doses up to 10 mg/kg i.p. was ineffective in classic tests for antidepressant activity. It neither antagonized the effects of reserpine in rats (hypothermia, ptosis) nor potentiated the effects of amphetamine (in mice and rats), nialamide or L-dopa (in mice) on locomotor activity. However, its antidepressant activitiy was found in the 'despair test' in rats. On the other hand, pizotifen inhibited the head twitch reaction induced by L-5-hydroxytryptophan in mice (ED50 = 0.009 mg/kg, i.p.) and by 5-methoxytryptamine (+ tranylcypromine) in rats (ED50 = 0.45 mg/kg, i.p.). It also antagonized tryptamine-induced clonic convulsions of fore-paws in rats (ED50 = 0.35 mg/kg, i.p.), and in doses of 5--10 mg/kg s.c. inhibited hyperthermia produced by LSD in rabbits. Finally, pizotifen (0.1--0.3 mg/kg, i.v.) inhibited or abolished LSD- or quipazine-induced stimulation of the hind limb flexor reflex of spinal rats; the above effect was not due to noradrenolytic action of the drug. These results suggest that pizotifen strongly blocks the central postsynaptic serotonin receptors.

Amphetamine↗

PubMed1980

Behavioural responses to stereotactically controlled injections of monoamine neurotransmitters into the accumbens and caudate-putamen nuclei.

Bilateral stereotactically-controlled injections of dopamine (5--50 micrograms of the hydrochloride salt) into the nucleus accumbens of nialamide-pretreated rats induced a marked stimulation of exploratory and locomotor activity, accompanied by intense sniffing and rearing. Conversely, bilateral injection of domapine (12.5--50 micrograms of the hydrochloride salt) into the caudate-putamen induced intense stereotyped activity which was dose-related. Both responses were blocked by IP haloperidol. Bilateral injection of noradrenaline (50 micrograms of the hydrochloride salt) into the accumbens nuclei did not produce any particular behavioural changes. The same injection into the caudate-putamen led to a moderate stimulation of stereotyped activity. Bilateral injection of 5-HT (50 micrograms of the bimaleinate salt) into the accumbens nuclei induced a moderate locomotor activity with some hole-dipping activity and sniffing; these behaviours were incoordinated and indecisive. The same injections into the caudate-putamen led to a moderate stimulation of locomotor activity and hole-dipping which was predominantly 'stereotyped' in character; on visual observation no other striking abnormalities were noted.

Animals↗

PubMed1980

Brain catecholamines modifications. The effects on memory facilitation induced by oxotremorine in mice.

the immediate posttrial injection of oxotremorine (0.250 mu Mol/kg, IP) can facilitate the retention of a passive-avoidance response in mice. After the administration of alfa-methyl-p-tyrosine methylester (alpha-MPT) by intracerebroventricular injection at doses that had no effect on retention (100 microgram, 10 microliter, 60 min before trial), the immediate posttrial injection of oxotremorine did not enhance retention. The employed dose of alpha-MPT reduced brain levels of norepinephrine by about 40% and those of dopamine by about 25%. Pretreatment with nialamide (30 mg/kg, 20h IP), which prevents the catecholamine depletion induced by alpha-MPT, counteracted the effects depletion induced by alpha-MPT, counteracted the effects of alpha-MPT on the actions of oxotremorine on retention. These results suggest a participation of brain catecholamines on the actions of oxotremorine on retention and a possible interaction of cholinergic neurons with catecholaminergic system in memory processes.

Animals↗

PubMed1975

The occurrence of the cell type containing a specific monoamine in the taste bud of the rabbit's foliate papila.

The fluorescence histochemical examination on biogenic amines of the rabbit's foliate papilla revealed that a specific monoamine exhibiting an yellow fluorescence was present in a certain cell type of taste buds. The fluorescence had the emission maximum at 520 mmu and faded rapidly under the influence of the UV-irradiation. The green fluorescence of adrenergic nerve had the emission maximum at 480 mmu and was fairly stable upon the UV-irradiation. The yellow fluorescence disappeared completely following reserpine treatment, while it was markedly enhanced by nialamide treatment. From the observations, it is suggested that certain taste bud cells of the foliate papilla contain a biogenic monoamine, probably 5-hydroxytryptamine (serotonin).

Animals↗