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At least 19 recordsLinked to original sources
PubMed1979

Effects of locally applied dopamine to the nucleus accumbens on the motor activity of normal rats and following alpha-methyltyrosine or reserpine.

The motor activity of rats was investigated following bilateral application of various doses (0--80 micrograms) of dopamine to the nucleus accumbens. A high dose (80 micrograms) of dopamine increased the motor activity of normal as well as alpha-methyltyrosine- and reserpine-treated rats. It also increased the late motor activity (6--9 min) of normal rats, probably due to stimulation of postsynaptic dopamine receptors. Lower doses (10--40 micrograms) of dopamine suppressed initial (0--3 min) motor activity of normal rats, perhaps due to stimulation of dopamine autoreceptors on the dopamine nerve terminals in the nucleus accumbens with a subsequent inhibition of dopamine neurotransmission. An intermediate dose (40 micrograms) of dopamine was able to restore the motor activity of alpha-methyltyrosine-treated but not of reserpine-treated rats at all time intervals. This difference, indicating a restoration of the normal pattern of habituation by dopamine only in animals pretreated with alpha-methyltyrosine, suggests that normal behaviour is dependent on release of dopamine by nerve impulses.

Animals↗
PubMed1977

Potentiation by alpha-methyltyrosine of the suppression of food-reinforced lever-pressing behaviour induced by antipsychotic drugs.

The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally - 4 hrs potentiates the effects induced by pimace, causing an alteration of the neuronal function.

Animals↗
PubMed1978

Failure of alpha-methyltyrosine to inhibit peripheral triiodothyronine formation.

To determine if the adrenergic nervous system, and specifically tyrosine hydroxylase, plays a role in the extrathyroidal conversion of T4 to T3, normal male volunteers were treated with T4 and subsequently with T4 and alpha-methyl-p-tyrosine (alpha-MPT), an inhibitor of tyrosine hydroxylase, for 2 weeks. The mean serum T4 and T3 concentrations increased during T4 administration and remained at the same levels during combined T4 and alpha-MPT administration. Urinary vanillylmandelic acid excretion declined significantly during alpha-MPT administration. These results do not support the hypothesis that tyrosine hydroxylase is involved in extrathyroidal T3 production.

Adult↗
PubMed1978

Effects of catecholamine depleting drugs and d-amphetamine on self-stimulation of the substantia nigra and locus coeruleus.

6-Hydroxydopamine treatments which preferentially depleted either norepinephrine or dopamine were used to define the importance of these transmitter systems in the behavioral alterations produced by catecholamine synthesis inhibitors and d-amphetamine on self-stimulation of the locus coeruleus and substantia nigra. After chronic reduction of brain dopamine, an acute depression of self-stimulation of both the locus coeruleus and substantia nigra occurred. Preferential depletion of norepinephrine with 6-hydroxydopamine did not result in a significant decrease in self-stimulation of locus coeruleus or substantia nigra. However, a dose of alpha-methyltyrosine wihch had no effect in control rats or in rats with brain norepinephrine depleted caused a significant reduction in responding at both electrode placements in animals depleted of brain dopamine. Administration of U-14,624 affected neither substantia nigra nor locus coeruleus self-stimulation, even though it produced an additional 70% depletion of norepinephrine. When d-amphetamine sulfate was given to 6-hydroxydopamine-treated rats, the facilitation of self-stimulation produced by this compound was significantly attenuated in rats with prior depletion of brain dopamine. Depletion of brain norepinephrine did not affect the actions of d-amphetamine on self-stimulation. In other experiments, the actions of d-amphetamine to increase self-stimulation of animals pretreated with reserpine was found to be antagonized by alpha-methyltyrosine but not by U-14,624. Results suggest that drugs can alter self-stimulation of a site in brain anatomically associated with noradrenergic neural pathways and self-stimulation of a site primarily associated with dopaminergic pathways in a similar manner. These data also provided evidence for the involvement of dopamine fibers in the pharmacological actions of d-amphetamine, reserpine and alpha-methyltyrosine.

Animals↗
PubMed1975

The effect of various amine-depleting drugs on the fever response exhibited by rabbits to bacterial or leucocyte pyrogen.

1 The concentration of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) in the rabbit brainstem was measured during fevers produced by either an injection of bacterial pyrogen (BP) or continuous infusion of leucocyte pyrogen (LP). 2 Both procedures had little effect on the concentration of noradrenaline in the preoptic/hypothalamic area but significantly (P smaller than 0.001) lowered the concentration of noradrenaline in the midbrain and pons/medulla. 3 BP significantly (P smaller than 0.01) lowered the concentration of 5-HT in the preoptic/hypothalamic area but had no effect in the midbrain or pons/medulla, whereas LP significantly (P smaller than 0.01) lowered the concentration of 5-HT in the midbrain and pons/medulla but had little effect in the hypothalamus. 4 The concentration of dopamine throughout the brainstem was little affected by either BP or LP fevers. However the concentration in the midbrain was significantly reduced by LP (P smaller than 0.001). 5 Alpha-Methyltyrosine (200 mg/kg) pretreatment diminished the pyrogenic response to both BP and LP whilst p-chlorophenylalanine (300 mg/kg) slightly enhanced the response to both forms of challenge. 6 Reserpine (1 mg/kg) diminished both types of fever whilst a combination of alpha-methyltyrosine and p-chlorophenylalanine slightly enhanced the fevers produced by either BP or LP. 7 The results obtained are discussed in relation to the mechanisms involved in the production of fever and to the possible function of noradrenaline and 5-HT as thermoregulatory transmitters.

Amines↗
PubMed1978

Effect of intraperitoneally administered GABA on the locomotor activity of mice.

Gammaaminobutyric acid (GABA) was injected intraperitoneally (i.p.) into mice at doses from 25--2000 mg/kg, and spontaneous locomotor activity was recorded for the following 20 min. A slight but significant decrease in the spontaneous locomotor activity was noted only with the highest dose. The stimulation of motor activity induced by ethanol (2.4 g/kg i.p.) was significantly counteracted by GABA (100 mg/kg i.p. and upwards). A further suppression of ethanol-induced hyperactivity was reached by pretreatment with aminooxyacetic acid (AOAA, 15 mg/kg i.p.). The stimulation of motor activity induced by morphine (10 mg/kg i.p.) remained unaffected by even high doses of i.p. GABA. Motility produced by activation of postsynaptic catecholamine receptors, i.e., by apomorphine (3 mg/kg i.p.) and clonidine (3 mg/kg i.p.) following reserpine (10 mg/kg i.p.) and alpha-methyltyrosine (250 mg/kg i.p.) pretreatment, was not affected by i.p. GABA injections, whereas hypomotility caused by a low dose of haloperidol (150 microgram/kg i.p.) was enhanced. In conjunction with earlier biochemical data, these results suggest a certain access of blood-borne GABA to the CNS, leading to inhibition of dopaminergic neurons involved in motility regulation.

Aminooxyacetic Acid↗
PubMed1977

Loss of histochemically demonstrable catecholamines in the glomus cells of the carotid body after alpha-methyl-para-tyrosine treatment.

A statistically significant decrease in the intensity of catecholamine fluorescence of some carotid body glomus cells was observed after inhibition of the enzyme tyrosine hydroxylase by injection of 80 mg/kg alpha-methyl-paratyrosine. The intensity of the formaldehyde-induced fluorescence was measured in individual glomus cells. The maximum decrease in the intensity was observed 4 to 6 hr after the alpha-methyltyrosine injection. This suggests a rapid turnover in the catecholamines of the carotid body.

Animals↗
PubMed1977

Suppression by GABAergic drugs of the locomotor stimulation induced by morphine, amphetamine, and apomorphine: evidence for both pre- and post-synaptic inhibition of catecholamine systems.

Locomotor stimulation induced in mice by morphine and amphetamine was antagonized by pretreatment with gamma-butyrolactone (GBL) and amino-oxyacetic acid (AOAA) at doses which had little effect on saline treated animals. The effects of morphine and AOAA on the turnover of brain catecholamines (CA) were determined by measuring both the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase and by measuring the depletion of noradrenaline (NA) after inhibition of tyrosine hydroxylase by alpha-methyltyrosine (alpha-MT). Morphine and AOAA were found to have opposite effects on CA turnover, i.e. morphine caused an increase and AOAA, a decrease. AOAA also antagonized the morphine-induced increase in CA turnover. These data might suggest that the well documented ability of GABAergic drugs to inhibit the firing of DA-containing neurons may be of importance in explaining the present findings. However, the locomotor stimulation induced by the directly-acting CA agonists, apomorphine and clonidine after pretreatment with reserpine and alpha-MT was also inhibited by the GABAergic drugs. It is therefore concluded that the suppressant effects of the GABAergic agents on hypermotility and not solely mediated by their effects on presynaptic CA mechanisms, but also by a postsynaptic inhibition at some point beyond the CA neurons.

4-Butyrolactone↗
PubMed1977

Effect of neurohumoral modulators on the morphine-induced hyperthermia in non-tolerant rats.

Wistar rats from one supplier have been shown to exhibit the atypical body temperature responses to morphine. In contrast to commonly used rats, in which morphine induced dose-dependent changes in body temperature, the initial administration of morphine (5, 10, 20, and 40 mg/kg, s.c.) to rats of this particular strain produced a consistent and prominent hyperthermia. This hyperthermia is mediated via an action on the typical morphine receptors since it was completely prevented by a specific narcotic antagonist, naloxone. Effects of neurohumoral modulators on the hyperthermia have been investigated in these rats. Pretreatment of animals with p-chlorophenylalanine, alpha-methyltyrosine, phenoxybenzamine or propranolol did not alter the hyperthermia. In contrast, the s.c. administration of 1 mg/kg of either tertiary or quaternary anticholinergic drug such as scopolamine, atrophine, methscopolamine and methylatropine significantly inhibited the hyperthermia. These results suggest that morphine causes hyperthermia in some strains of rats by a cholinergic mechanism and the involvement of an adrenergic or serotonergic mechanism in this case appears unlikely.

Animals↗
PubMed1976

The startle response in rats: effect of ethanol.

The effects of acute and chronic ethanol intake on the startle response was examined in male rats. Ethanol given IP produced a dose-dependent decrease in the amplitude of the startle response measured 30 min later. With a dose of 1 g/kg, the effect was evident at 15 min and had recovered substantially by 60 min. The effect of ethanol on the startle response was potentiated by pretreatment of the animals with pimozide, haloperidol, and p-chlorophenylalanine but not by propranolol, phenoxybenzamine, alpha-methyltyrosine, or pargyline. After 3 weeks on an ethanol-containing diet, the startle response was greater than that shown by rats on the control iso-caloric, sucrose-containing diet. After ethanol withdrawal, the startle response was further increased, with a peak about 9 to 12 hr after discontinuation of ethanol; thereafter, the response declined. This time course of heightened startle response during ethanol withdrawal corresponds to the time course of the activation of noradrenergic neurons during withdrawal. It appears that dopaminergic and serotonergic neurons are involved in the mediation of the startle response in rats.

Adrenergic alpha-Antagonists↗
PubMed1978

Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants.

3,3-Diphenylcyclobutylamine (4), N-methyl-3,3-diphenylcyclobutylamine (6), and N,N-dimethyl-3,3-diphenyl-cyclobutylamine (7) have been prepared and tested as potential antidepressant agents. The secondary (6) and tertiary (7) amines strongly decrease the accumulation of NA and 5-HT in brain slices in vitro and in vivo. The cyclobutylamines also cause motor stimulation. The most potent compound in this respect is the tertiary amine 7. The increase in locomotion is not blocked by pretreatment with phenoxybenzamine, methergoline, or alpha-methyltyrosine. Pretreatment with pimozide or reserpine reduces the hyperactivity induced by 7. This hyperstimulation seems to be caused by a mechanism of action which differs from that of amphetamine. 7 may cause increase in locomotion by release of dopamine from granular stores.

5-Hydroxytryptophan↗
PubMed1977

Biochemical differentiation of amphetamine vs methylphenidate and nomifensine in rats.

Amphetamine-like stimulants were divided into two groups, one in which the stereotyped behaviour was not antagonized by reserpine [(+)-amphetamine, (-)-amphetamine, methamphetamine, phenmetrazine and phenethylamine] and another group in which the behavioural effects were blocked by reserpine (methylphenidate, nomifensine, pipradrol and amfonelic acid (NCA; Win 25978)). Both groups increased homovanillic acid (HVA) in whole brain 2 h after administration. The 'methylphenidate group' also increased brain 3,4-dihydroxyphenylacetic acid (DOPAC) in naive rats; whereas the '(+)-amphetamine group' decreased DOPAC in naive rats, as well as in reserpinized rats, alpha-methyl-p-tyrosine-treated rats and after acute hemisection. The reserpine antagonism of the 'methylphenidate group'-induced stereotyped behaviour was partially reversed by type A monoamine oxidase inhibition. The '(+)-amphetamine group'-induced stereotyped behaviour was not blocked by short time pretreatment with alpha-methyltyrosine, only by longer pretreatment intervals. The mechanisms by which the two groups are differentiated biochemically is discussed with special attention to possible intra-neuronal inhibition of dopamine oxidation by the '(+)-amphetamine group'.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

Thyrotropin-releasing hormone: hyperactivity and mesolimbic dopamine system in rats.

The mechanism of stimulatory action of thyrotropin-releasing hormone (TRH) on spontaneous motor activity was investigated in rats. TRH produced a significant hyperactivity with intraperitoneal administration of 20 mg/kg or bilateral injection of 10 micrograms into the nucleus accumbens septi (NAS). Following bilateral injection of 6-hydroxydopamine into the mesolimbic dopamine (DA) pathway, the hyperactivity induced by TRH was not altered, whereas the response to apomorphine given intraperitoneally or DA injected into the NAS was clearly enhanced. The TRH-induced hyperactivity was remarkably suppressed by alpha-methyltyrosine and in contrast, augmented by pargyline. Systemic injection of aminooxyacetic acid in a dose producing behavioral depression reduced markedly the TRH-induced hyperactivity. Bilateral injection of ethanolamine O-sulphate (100 micrograms) into the NAS produced no behavioral depression per se, but remarkably attenuated the hyperactivity response to TRH or DA (20 micrograms) given intraperitoneally or into the NAS. Both TRH (10(-5) and 10(-4) M) and methamphetamine (10(-6)--10(-4) M increased the spontaneous release of 14C-DA from rat NAS slices. These findings suggest that TRH induces hyperactivity by enhancing DA release from nerve terminals in the NAS without a direct stimulation of the post-synaptic DA recptors. TRH and GABA, independently or via interaction between them, may play a reciprocal regulatory role in the activity of the mesolimbic DA system.

Animals↗
PubMed1977

Reduced inactivation of tyrosine aminotransferase in the prefused rat liver in the presence of ethanol.

The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally -- 4 hrs potentiates the effects induced by pimozide (0.04 mg/kg intraperitoneally -- 6 hrs) which preferentially blocks central dopamine (DA) receptors, but not the effects induced by phenoxybenzamine (0.5 mg/kg intraperitoneally -- 30 min.) which blocks central noradrenaline (NA) receptors. Furthermore, the behavioural suppression induced by chlorpromazine (0.5 mg/kg intraperitoneally -- 15 min.), thioridazine (1.5 mg/kg intraperitoneally -- 15 min.), or haloperidol (0.02 mg/kg intraperitoneally -- 15 min.) were not potentiated by the administration of the inhibitor of DA-beta-hydroxylase, bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA-63) 4 mg/kg subcutaneously -- 1 hr). The potentiation by alpha-MT of the clinical effects of antipsychotic drugs and of their behavioural effects in animal experiments is in all probability due to a blockade by alpha-MT of a feed-back mediated compensatory increase in the catecholamine synthesis as a result of a blockade of central NA and/or DA receptors by the antipsychotic drugs. Since, in the present experiments, the behavioural effects induced by drugs which block central DA but not NA receptors were potentiated by the simultaneous administration of alpha-MT, it seemed probable that the disruption of conditioned behaviours by antipsychotic drugs is due to a blockade of central DA receptors. In view of the fact that the ability to selectively disrupt conditioned behaviours is shared by a wide range of antipsychotic drugs differing in chemical structure and also in their mode of action, it is possible that a blockade of DA neurotransmission is also of primary importance for the clinical effects induced by antipsychotic drugs.

Acetaldehyde↗
PubMed1977

The actions of amphetamine on neurotransmitters: a brief review.

The central stimulant actions of d-amphetamine are not altered in animals in which brain stores of catecholamines have been depleted with reserpine, but they are blocked by alpha-methyltyrosine, which inhibits catecholamine synthesis. The results of a variety of experiments suggest that the central actions of amphetamine result primarily from the ability of the drug to facilitate the release of newly synthesized dopamine from nerve terminals in the forebrain. The results of experiments in animals in which dopaminergic nerve terminals in various brain regions have been selectively destroyed by intracranial microinjection of 6-hydroxydopamine reveal that the locomotor stimulant actions of relatively low doses of amphetamine are dependent upon mesolimbic dopaminergic neurons, whereas the stereotyped behaviors induced by relatively larger doses of amphetamine are dependent upon nigrostriatal dopaminergic neurons. The central actions of amphetamine appear to be the primary result of interactions with dopamine neurons, but secondarily the drug also alters the dynamics of other putative neurotransmitters (e.g. acetylcholine, 5-hydroxytryptamine) in the brain.

Amphetamine↗
PubMedDate not supplied

[Effect of several neuroleptic, adreno-, sympatho- and cholinolytic substances on the development of experimental cerebral edema induced by nicotine].

The influence of some neuroleptic, adreno, sympatho- and cholinolytic substances on the development of experimental brain edema induced with nicotine was studied in tests conducted on rats. It was ascertained that marked antiedemic properties display drugs blocking the alpha-adrenoreceptors (phentolamine, dopegit), the neuroleptic chlorpromazine and central M-cholinolytics (benactizine). Weak action exert central H-cholinolytics (difacil trasentin) and the neuroleptic galoperidol. Sympatho- and beta-adrenolytics (guanethidine, alpha-methyltyrosine, obsidan), and also the neuroleptic triphthazine fail to prevent the development of an experimental brain edema. It is presumed that a brain edema induced with nicotine comes as a result of the catecholamines liberation and is also due to stimulation of alpha-adrenoreactive systems.

Animals↗
PubMedDate not supplied

The effect of alpha-adrenolytics on central action of agonists and antagonists of dopaminergic system.

alpha-Adrenoceptor blocking agents: phenoxybenzamine, phentolamine and aceperone, potentiated and prolonged amphetamine and apomorphine stereotypy in the rat, but inhibited the amphetamine hypermotility. The hypermotility produced by apomorphine was antagonized only by aceperone. Cataleptogenic action of haloperidol and fluphenazine was inhibited by the alpha-adrenoceptor blocking agents. Phenoxybenzamine and phentolamine, and to a smaller degree aceperone, inhibited the depletion of dopamine following pretreatment of rats with alpha-methyltyrosine. The results indicate that the blockade of central alpha-adrenergic receptors changes the reactivity of dopaminergic system on the action of its agonists and antagonists.

Adrenergic alpha-Antagonists↗