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At least 451 records · Page 25Linked to original sources

PubMed1995

Serotonergic and non-serotonergic projections from the raphe nuclei to the piriform cortex in the rat: a cholera toxin B subunit (CTb) and 5-HT immunohistochemical study.

Retrograde axonal transport of the cholera toxin B subunit (CTb) was combined with 5-HT immunohistochemistry to determine the origin of the serotonergic innervation of the piriform cortex (PC) in the rat. After iontophoretic CTb injections in the PC, a substantial number of retrogradely labeled cells were found in the middle and medio-ventral part of the dorsal raphe nucleus (RD). A few retrogradely labeled cells were also observed in the median raphe nucleus (MnR) and the B9 serotonergic cell groups. Following CTb and 5-HT immunohistochemistry on the same sections, double-labeled cells were observed in the RD, MnR and B9 groups. In the RD, 30% of CTb stained cells were immunoreactive to 5-HT. After colchicine or nialamide (a monoamine oxidase inhibitor) pretreatment the percentage of these double-labeled cells reached 70%. These results indicate that both 5-HT and non-5-HT neurons in the RD innervate the PC and that the percentage of double-labeled cells is influenced by drug pretreatment. To determine the terminal fields of the RD efferent fibers in the PC, injections of the anterograde tracer PHA-L were also performed. Analysis of the fiber distribution in the PC further revealed some medio-lateral and antero-posterior differences.

Animals↗

PubMed1979

Studies on the distribution and metabolism of N-[14C]nitrosopyrrolidine in mice.

Pretreatments with pyrazole, ethanol, nialamide or diethyldithiocarbamate were found to strongly depress the exhalation of 14CO2 and the incorporation of radioactivity in the acid-insoluble fraction of the liver in mice injected with N-[14C]nitrosopyrrolidine. Whole-body autoradiography performed with hemisections of mice at -80 degrees C (to prevent evaporation of the volatile N-nitrosopyrrolidine) and with dry tape-sections (to localize the non-volatile metabolites), using pretreated and non-pretreated mice, indicated a uniform distribution of the non-metabolized N-nitrosopyrrolidine in the tissues. At the shortest survival intervals (1 and 5 min), a high level of metabolites were found in the liver, the tracheo-bronchial and nasal mucosa and Harder's gland, indicating a local formation of metabolits in these tissues. At later survival intervals (0.5--24 h) metabolites were in addition found in tissues with a rapid cell turnover and a high rate of protein synthesis and in brown fat, which probably reflects incorporation of metabolites via normal biosynthetic pathways. Autoradiography of N-[14C]nitrosopyrrolidine in mice given the substance orally resulted in distribution pictures similar to those obtained after i.v. injections.

Animals↗

PubMed1975

Effects of penfluridol and other drugs on apomorphine-induced stereotyped behavior in monkeys.

The effects of some drugs on apomorphine-induced stereotyped behavior were studied in male cynomolgus monkeys. Apomorphine produced the dose-dependent stereotyped behavior characterized mainly by continuous licking and biting, and repetitive movements of the hands, head and body in the monkeys. Penfluridol as well as haloperidol showed a clear antagonistic effect on the apomorphine-induced stereotyped behavior, while chlorpromazine was less antagonistic than haloperidol. The antagonistic effect of penfluridol lasted longer than that of haloperidol. Reserpine did not inhibit the apomorphine-induced stereotyped behavior though the drug elicited markedly the behavioral depression and alpha-methyl-p-tyrosine also did not block the stereotyped behavior. Nialamide did not depress the apomorphine-induced stereotyped behavior. In provoking the stereotyped behavior in monkeys, apomorphine probably acts directly on dopamine receptors in the extrapyramidal system, and penfluridol is suggested to act as a dopamine receptor blocker with a long action. The results indicate that protection against apomorphine-induced stereotyped behavior in monkeys may be a useful method for evaluating neuroleptic drugs.

Animals↗

PubMedDate not supplied

Neuroleptic antagonism of dyskinetic phenomena.

The bilateral intrastriatal administration of dopamine to guinea pigs pretreated with nialamide-induced dyskinesias characterized by gnawing, biting and licking reactions, acute twisting of the head and neck, whole body or head and neck rocking movements, and a hyperactive state. Hyperactivity was inhibited by the peripheral administration of large doses of many neuroleptic agents, e.g. haloperidol, fluphenazine, but only pimozide and oxiperomide inhibited the other forms of dyskinetic movements. This was not due to a peculiar depressant effect of these agents in the guinea pig since haloperidol was shown to be equipotent to oxiperomide and of greater potency than pimozide both in causing catalepsy and antagonising amphetamine sterotypy...

Adrenergic alpha-Antagonists↗

PubMed1977

Effects of levodopa and dopamine of plasma glucose concentration in mice.

In nialamide-treated, fasted mice levodopa produced a dose-dependent hypoglycaemic response. The response was also seen in pargyline-treated mice but not in animals which were not treated with a monoamine oxidase inhibitor. Dopamine did not affect plasma glucose under these conditons. In doses which were ineffective when injected i.v., both levodopa and dopamine produced hypoglycemia when injected intracerebroventriculary (i.c.v.). The hypoglycaemic response to levodopa was prevented by the dopamine antagonists, haloperidol and pimozide. The possible involvement of 5HT in the hypoglycaemic response to levodopa was suggested by the blockade of the response by cyproheptadine and methysergide together with the observations that hypoglycaemia is produced by 5HTP and by i.c.v. 5HT. p-Chlorophenylalanine (PCPA) also reduced the response to levodopa but the usefulness of PCPA as an inhibitor of 5HT synthesis in these experiments in doubtful since it also inhibited the hypoglycaemic effects of 5HTP and i.c.v. 5HT. Hypoglycaemia produced by levodopa did not appear to involve stimulation of insulin secretion since plasma IRI levels were not increased by levodopa and the hypoglycaemia was accompanied by a elevation of plasma FFA and no significant change in the liver glycogen content. It is suggested that the hypoglycaemic effect of levodopa is mediated through dopamine acting in the brain, although the involvement of 5HT in the response and the mechanisms involved remain to be determined.

Animals↗

PubMed1977

Differential activation by some 2-aminotetralin derivatives of the receptor mechanisms in the nucleus accumbens of rats which mediate hyperactivity and stereotyped biting.

A series of 2-aminotetralin derivatives were injected into the nucleus accumbens of rat to assess the nature of the dopamine mechanisms in this nucleus which modulate hyperactivity and stereotyped behaviour. It was shown that (1) Derivatives with either 5,6- or 6,7-dihydroxy substitutions were each able to induce hyperactivity and stereotyped behaviour, but substitutions in the 5,6-positions conferred greater potency throughout the series. This differential was emphasised by the continued activity of 2-amino-5,6-dihydroxytetralin in the absence of nialamide whilst the action of 2-amino-6,7-dihydroxytetralin was greatly reduced. (2) The hydroxyl functions in both the 5,6- and 6,7-series were essential for activity: dimethyoxy derivatives were inactive. (3) Generally, substitution of the nitrogen atom with one or two methyl groups, or with a butyl group, reduced or abolished activity. However, N-ethyl and N-propyl substitution markedly enhanced stereotypic potential in the 5,6-dihydroxy series (but not in the 6,7-series). The N-isopropyl derivative in the 5,6-series reflected the activity of the N-propyl compound but a further substitution of the N atom with the methyl group (N-isopropyl-N-methyl) greatly reduced the stereotypic potential without modification of the hyperactivity response. In contrast, N,N-dipropyl substitution abolished the hyperactivity response whilst increasing sterotypic potential. (4) alpha and beta-adrenoceptor blocking agents and alpha-methyl-p-tyrosine failed to reduce the hyperactivity induced by 2-amino-5,6-dihydroxytetralin or the stereotyped behaviour induced by 2-(N,N-dipropyl)-amino-5,6-dihydroxytetralin. Both behaviours were, however, very sensitive to blockade by haloperidol, indicating that both the hyperactivity and stereotyped responses are dopamine-dependent. It is concluded that the dopamine mechanisms in the nucleus accumbens which mediate/regulate hyperactivity and stereotyped behaviour are different. Further, it is suggested that the 2-aminotetralins may be valuable tools in studies designed to assess the topography of cerebral dopamine systems.

2-Naphthylamine↗

PubMed1987

Drug-induced penile erections in rats: indications of serotonin1B receptor mediation.

The induction of penile erections by a variety of compounds with a direct or indirect effect on serotonin (5HT) receptors was investigated in rats. L-5-Hydroxy-tryptophan (L-5HTP) induced penile erections when co-administered with nialamide and the peripheral decarboxylase inhibitor benserazide, indicating that the site of action for inducing penile erections is within the central nervous system. Penile erections were also induced by the 5HT uptake inhibitors zimelidine, fluoxetine, citalopram, Org 6997, by the 5HT-releasing agent fenfluramine and by the putative 5-HT1B receptor agonist 1-(3'-chlorophenyl)-piperazine (mCPP). The 5HT1A-agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) did not induce penile erections. The less selective 5HT receptor agonists 5-methoxy-N,N-dimethyl-tryptamine (5MeODMT), 5-methoxytryptamine (5MeOT), dl-lysergic acid diethylamide (LSD) and Ru 24969 were also ineffective. Induction of penile erections by quipazine appeared only when this compound was co-administered with the 5HT2 receptor antagonist pirenperone. Receptor antagonists were tested against penile erections induced by Org 6997. The beta-adrenoceptor antagonists that also have 5HT1 antagonistic properties, (S)-pindolol and dl-propranolol, antagonized Org 6997-induced penile erections but butoxamine and metoprolol did not. Spiperone and pirenperone in doses selective for 5HT1A and 5HT2 receptors respectively were also inactive. Haloperidol, 0.46 mg/kg, partially attenuated penile erections induction. The data are discussed in the light of the hypothesis that penile erections induction by serotonin-mimetic compounds is mediated by 5HT1B receptors in the striatum.

5-Hydroxytryptophan↗

PubMed1984

L-dopa-induced locomotor-like activity in ankle flexor and extensor nerves of chronic and acute spinal cats.

The ability of L-DOPA and nialamide to produce locomotor-like rhythmic discharges (fictive locomotion) in hind limb nerves of acute and chronically spinalized and paralyzed cats was examined. Ankle flexor and extensor nerves of chronic cats exhibited pharmacologically induced alternate bursts of activity that had significantly shorter cycle times and burst durations than those produced in ankle flexor and extensor nerves of acutely prepared cats. Furthermore, prior to pharmacologic activation, both ankle flexor and extensor nerves of chronic preparations frequently exhibited spontaneous alternate bursts of activity. Neuronal discharges from nerves of chronic preparations, both prior to and after pharmacologic activation, exhibited much greater variability in both cycle time and burst duration compared with those observed in acute preparations.

Action Potentials↗

PubMed1988

Effect of 5-hydroxytryptamine on the rate of cerebrospinal fluid production in rabbit.

Infusion of 5-hydroxytryptamine in mock cerebrospinal fluid of rabbits lowered cerebrospinal fluid production dose-dependently by nearly 30%. The effect was amplified in the presence of the monoamine oxidase inhibitor, nialamide. The 5-hydroxytryptamine-induced inhibition was partly counteracted by ketanserin, and further addition of practolol completely blocked the reduction in cerebrospinal fluid formation, suggesting that both 5-hydroxytryptamine receptors and beta 1-adrenergic receptors were involved in the response mediated by both the secretory epithelium and the vascular bed of the plexus.

Animals↗

PubMed1985

Multiple opiate receptors may be involved in suppressing gamma-aminobutyrate release in substantia nigra.

Slices of rat substantia nigra were preloaded with tritiated gamma-aminobutyrate (GABA) or dopamine (DA) and perfused with Krebs solution containing 5 microM aminooxyacetic acid or 10 microM nialamide to inhibit the catabolism of GABA and DA respectively. Repeated brief exposures to high potassium medium (+ 30 mM K+ for 1 min) evoked a consistent pattern of calcium-dependent 3H efflux against which the effects of opiates (10-400 microM) were assessed. Opiate agonists inhibited K+-induced 3H-GABA efflux in the following decreasing order of potency: bremazocine greater than D-Ala2-Met5-enkephalinamide (ENK) greater than SKF 10047 much greater than morphine, consistent with the participation of kappa, delta, sigma and to a lesser extent mu opiate receptors respectively. Naloxone (1 microM) partially antagonised the response to morphine and ENK, while ICI 154129 attenuated ENK only. Save for a GABA-releasing action of SKF 10047 at high doses, none of the compounds altered basal outflow of 3H-GABA. Naloxone, in the dose range 10-400 microM, also significantly inhibited depolarisation-induced release of 3H-GABA. In parallel experiments none of the compounds tested were found to influence 3H-DA release in concentrations up to 40 microM, but thereafter suppressed K+-induced 3H-DA outflow indiscriminately. The results are discussed with reference to the possible mechanism(s) via which injected and endogenous opiates may affect motor performance by attenuating GABA transmission in the nigra.

Aminooxyacetic Acid↗

PubMed1985

Effects of antidepressant drugs on a quickly-learned conditioned-suppression response in mice.

Mice experienced to electric shock, exhibited a marked suppression of motor activity when placed in the same cage 24 hr after administration of shocks. Acute administration of imipramine-HCl (10 mg/kg, i.p.), desipramine-HCl (5 and 10 mg/kg, i.p.) and amitriptyline-HCl (5 and 10 mg/kg, i.p.) caused marked reduction of the conditioned suppression of shocked mice, but reduced the motor activity of the non-shocked mice. Maprotiline, mianserin and dimetacrine did not cause reduction of the conditioned suppression. Nialamide (100 mg/kg, i.p.) and pargyline-HCl (100 and 200 mg/kg, i.p.) caused marked reduction of the conditioned suppression but did not increase the motor activity of the non-shocked mice, and tranylcypromine-HCl (10 and 20 mg/kg, i.p.) did not cause reduction of the conditioned suppression. Diphenhydramine-HCl (10 and 20 mg/kg, i.p.) reduced the conditioned suppression of shocked mice in a dose-related manner. Chronic administration of imipramine-HCl (1 and 5 mg/kg, i.p.) for 14 days significantly reduced the conditioned suppression but did not influence the motility rate of the non-shocked mice. Also, chronic administration of amitriptyline (1 mg/kg, i.p.), desipramine (5 mg/kg, i.p.) and dimetacrine (10 mg/kg, i.p.), for 10 days, significantly reduced the conditioned suppression, but did not influence the motility rate of the non-shocked mice. Chronic administration of maprotiline reduced the conditioned suppression. On the other hand, chronic administration of mianserin (5 mg/kg, i.p.) and diphenhydramine (10 mg/kg, i.p.) did not cause a reduction of the conditioned suppression.

Acridines↗

PubMed1980

Tube running activity in mice: a method to evaluate the behavioural effects of drugs.

A new method to study locomotor activity in mice has been developed. The time it takes for a mouse to run 100 cm in a narrow tube is measured. In the present study the effects of various environmental factors on this tube running activity have been examined. The most important factor was found to be the frequency of testing. With repeated testing the run time was increased, which probably is due to a decrease in exploratory activity. However, tube running seems not to be a specific measure of exploratory activity. Administration of nialamide alone (50-200 mg/kg IP) as well as combined with 5-hydroxy-DL-tryptophan (6.25-25 mg/kg IP) gave a dose measuring 5-hydroxy-tryptamine mediated behaviour.

5-Hydroxytryptophan↗

PubMed1986

Stimulatory effect of N-methyl aspartate on locomotor activity and transmitter release from rat nucleus accumbens.

N-Methyl-aspartate (NMA), an agonist at central glutamate receptors, elicited prolonged and intense locomotor activity when injected into the nucleus accumbens septi (NAS) in subconvulsive doses (3-10 micrograms bilaterally). This effect was antagonised by intra-accumbens injection of the specific NMA antagonist, aminophosphonovaleric acid (APV) in a dose (3.0 micrograms bilaterally) that was without intrinsic effect when given on its own. Intra-accumbens injection of APV also suppressed locomotor hyperactivity elicited by intra-accumbens injection of DA (50 micrograms bilaterally) in rats pretreated with nialamide. In vitro release of [3H]-acetylcholine in accumbens tissue slices was significantly increased in the presence of NMA (30 microM) or N-methyl-D-aspartate (NMDA) (15 microM). Both effects were antagonised by APV (30 microM). Similar results were obtained with tissue slices of rat corpus striatum. These results suggest that locomotor stimulation by intra-accumbens NMA is mediated by an action on the mesolimbic dopaminergic neuron, either directly or via a cholinergic interneuron. In addition, activity at the glutamate synapse may be enhanced by the presence of DA affecting glutamate release and/or reuptake.

2-Amino-5-phosphonovalerate↗

PubMed1986

The lesion of serotonergic neurons does not prevent antidepressant-induced reversal of escape failures produced by inescapable shocks in rats.

The present study was aimed at testing the hypothesis (based mainly on biochemical evidence) of the implication of brain serotonergic neurons in the induction of learned helplessness (escape deficit) and its reversal by antidepressants in rats. After desipramine (25 mg/kg IP)-pretreatment rats were either sham-operated or infused with 5,7-dihydroxytryptamine (5,7-DHT, 3 micrograms of free base in 0.4 microliter saline containing 0.02% ascorbic acid) into the midbrain raphe area. Three weeks later, experimental animals were exposed to 60 randomized inescapable shocks (0.8 mA; 15 sec duration), control rats being not shocked, and 48 hr later, they were subjected to daily shuttle-box sessions (30 trials/day; ITI = 30 sec) on 3 consecutive days in order to assess escape deficits. After inescapable shock pretreatment separate groups of rats were given twice daily injections of clomipramine (total daily dose: 32 mg/kg), desipramine (24 mg/kg), imipramine (32 mg/kg), nialamide (32 mg/kg) or saline. After behavioral testing, animals were sacrificed, and tryptophan hydroxylase activity was assayed in the cerebral cortex, the hippocampus and the striatum. We found that damage to serotonergic neurons associated with a 70% loss of tryptophan hydroxylase activity altered neither escape deficits produced by prior exposure to inescapable shock, nor the ability of either antidepressant studied to reverse escape failures in the shuttle-box paradigm. These findings cast some doubts on the hypothesized crucial role of serotonergic neurons in helpless behavior and its reversal by antidepressants.

Animals↗

PubMed1987

Studies on the central action of L-threo-3,4-dihydroxyphenyl-serine (L-threo-DOPS) in FLA-63-treated mice.

In order to clarify the central action of L-threo-DOPS, the effect of benserazide on behavioral and biochemical changes by L-threo-DOPS in FLA-63-treated mice was studied. L-threo-DOPS in combination with nialamide markedly increased both the locomotor activity and the concentrations of the brain, heart and kidney norepinephrine (NE) in the FLA-63-treated mice. Benserazide at low doses did not alter either the rise of the brain NE level or the increase in locomotor activity, whereas it significantly inhibited the rise of the heart and kidney NE levels. Benserazide at a high dose significantly inhibited all of them. These results suggested that the increase in locomotor activity might be mediated via activation of the central noradrenergic neurons system by L-threo-DOPS.

Animals↗

PubMed1986

The presence of extraganglionic fluorescent neurons in the myenteric plexus of the guinea pig small intestine.

Fluorescent histochemical observations of the small intestine of the guinea pig demonstrated that single fluorescent cell bodies, separate from the ganglia, were present in the myenteric plexus. These cell bodies gave rise to single processes which entered the ganglia or the interganglionic strands. They were of a very small size, and the intensity of their fluorescence increased by pretreatment with L-DOPA and nialamide. Interruption of extrinsic nerve pathways to the small intestine caused a disappearance of the meshwork of fluorescent fibers in the myenteric plexus; but in some areas a fluorescent fiber which supplied its terminal to the ganglion was seen to remain. A photograph taken from the denervated myenteric plexus revealed that a long process arising from an extraganglionic cell entered the ganglion and ramified into terminal branches.

Animals↗

PubMed1979

Melatonin-and serotonin-stimulated release of vasopressin from rat neurohypophysis in vitro.

In order to study the control of vasopressin-release, the effect of a series of potential agents was studied in an in vitro perifusion system of rat neurohypophysis after in vivo treatment with nialamide, a monoamine oxidase inhibitor. In this system, metlatonin stimulated vasopressin-release in a dose-dependent manner (1 x 10-8 to 1 x 10-3 M). Serotonin (1 x 10-3 M) also led to a significant increase of vasopressin-release whereas quipazine (1 x 10-3 M), a putative serotonin agonist and monoamine oxidase inhibitor, caused a 3-fold stimulation of the release of the neurohormone. The stimulatory effects of melatonin and serotonin were prevented by omission of Ca2+ combined to an excess of Mg2+ (12mM) in the perifusion medium. 1 x 10-6 M somatostatin did not affect basal or melatonin-stimulated vasopressin-release. These results show that melatonin and serotonin can have a direct stimulatory effect on vasopressin release at the neurohypophyseal level.

Animals↗

PubMed1979

On the presence of extraneuronal catecholamine in the iris of the rat: a scanning microfluorimetric study.

Formaldehyde-induced fluorescence (FIF) of noradrenalin (NA) was studied in histochemical preparations of the rat iris. With the aid of a two-dimensional microfluorimetric scanning method, quantitative information was obtained from neuronal and non-neuronal elements selectively. Spectral analysis and fluorimetric studies showed the existence of extraneuronal NA in the iris of untreated rats. Surgical and pharmacological (reserpine, amphetamine, imipramine, nialamide) manipulation of sympathetic neurotransmission-induced changes in extraneuronal fluorescence, which did not parallel changes in fluorescence of neuronal elements. A positive relationship was found between changes in extraneuronal fluorescence and the postsynaptic effect (pupil diameter). We hypothesize that extraneuronal catecholamine (CA) fluorescence is a histochemical parameter for synaptic neurotransmission.

Animals↗