A model for the quantitative study of central dopaminergic and serotoninergic activity

Bieger, D.; Larochelle, L.; Hornykiewicz, Oleh

doi:10.1016/0014-2999(72)90140-9

Cited by 63 publications

(30 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dopamine-sensitive adenylate cyclase of the caudate nucleus is also weakly antagonized by a-adrenergic, but not by 3-adrenergic, blocking agents. Finally, the ability of apomorphine both to mimic the actions of dopamine upon the "dopamine receptor" of the caudate nucleus (7,16) and to stimulate the adenylate cyclase activity of the caudate nucleus supports the idea that the dopamine-sensitive adenylate cyclase of the caudate nucleus is the "dopamine receptor" that has been characterized by others.…”

supporting

confidence: 61%

See 1 more Smart Citation

Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine receptor”

Kebabian

Petzold

Greengard

1972

Proc. Natl. Acad. Sci. U.S.A.

819

197

View full text Add to dashboard Cite

An adenylate cyclase that is activated specifically by low concentrations of dopamine has been demonstrated in homogenates of caudate nucleus of rat brain. A half-maximal increase in the activity of the enzyme occurred in the presence of 4 ,M dopamine. Concentrations of dopamine as low as 0.3 MAM stimulated the activity of the enzyme. The adenylate cyclase activity of the homogenates was also stimulated by low concentrations of apomorphine, a substance known to mimic the physiological and pharmacological effects of dopamine. The Recent work has implicated dopamine as a neurotransmitter in the basal ganglia of the mammalian brain (1-4). In addition, a variety of behavioral and pharmacological evidence supports the concept of a "dopamine receptor" within the basal ganglia (5-7). Moreover, evidence has accumulated that Parkinsonism can result either from depletion of the dopamine in the basal ganglia or from blockade of the "dopamine receptor" (1, 3). It would, therefore, seem of considerable importance to identify the biochemical receptor with which dopamine interacts in the basal ganglia.Recent studies on the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in ganglia of the peripheral sympathetic nervous system have led to a partial clarification of the role and mechanism of action of dopamine within these peripheral ganglia. An adenylate cyclase was demonstrated in these ganglia that was specifically stimulated by very low concentrations of dopamine (8). The demonstration of this enzyme in these ganglia, together with other evidence presented elsewhere (9-12), led to the suggestion that cyclic AMP mediates dopaminergic transmission, and thereby modulates cholinergic transmission within these ganglia. More recently, a dopamine-sensitive adenylate cyclase has been reported by Brown and Makman (13) in mammalian retina, where dopaminergic amacrine cells occur. It seemed possible, particularly in view of the known balance and interaction of cholinergic and dopaminergic mechanisms in the extrapyramidal system, that a dopamine-sensitive adenylate cyclase might mediate dopaminergic transmission in the basal ganglia, with consequent modulation of cholinergic transmission. Therefore, we undertook a search for such an enzyme in the caudate nucleus. We report the results of these studies, which demonstrate the occurrence of this enzyme, and describe some of its pharmacological properties. The similarities between the pharmacological properties of this enzyme and those of the "dopamine receptor" suggest a close relationship between these two entities. METHODS Male Sprague-Dawley rats, weighing about 200 g, were killed by decapitation. The brain was rapidly excised in a cold room (40) and placed in cold Krebs-Ringer bicarbonate buffer that contained (in mmol/liter): NaCl, 122; KC1, 3; MgSO4, 1.2; CaCl2, 1.3; KH2PO4, 0.4; NaHCO3,25;10. This buffer had previously been equilibrated with a gas mixture of 95% 02-5% C02, and had a pH of 7.4 at 250. The brainstem and cerebellum were removed, and the brain was he...

show abstract

supporting

confidence: 61%

“…Low concentrations of either haloperidol or chlorpromazine antagonize the physiological and pharmacological effects of dopamine and norepinephrine within the caudate nucleus (5,6,7,25), and also abolish the increased adenylate cyclase activity due to either of the catecholamines.…”

mentioning

confidence: 99%

Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine receptor”

Kebabian

Petzold

Greengard

1972

Proc. Natl. Acad. Sci. U.S.A.

819

197

View full text Add to dashboard Cite

show abstract

“…Methysergide, a drug claimed to block 5-hydroxytryptamine receptors (Bieger, Larochelle & Hornykiewicz, 1972), did not cause any consistent or dose-dependent effect on either apomorphine or amphetamine-induced circling behaviour. However there is doubt as to how well this drug penetrates into the brain (Doepfner, 1962), although it enhances apomorphine-induced locomotor activity (Grabowska & Michaluk, 1974) and stereotypy and apomorphine-induced turning in rats (Baldessarini et al, 1975).…”

Section: Discussionmentioning

confidence: 99%

Effects of Drugs Acting on Cerebral 5‐hydroxytryptamine Mechanisms on Dopamine‐dependent Turning Behaviour in Mice

Milson¹,

Pycock²

1976

British J Pharmacology

View full text Add to dashboard Cite

I The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2 Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3 Parachlorophenylalanine (3 x 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4 Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025-0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6 The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5-hydroxytryptamine. 7 The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed.

show abstract

“…In the present studies another specific 5-HT uptake inhibitor, fluoxetine (Wong et al 1974;Fuller, Perry & Molloy, 1975) The activation of MTA induced by 5-HTP appears to be different from that observed after PMA treatment. Although activation of MTA by both 5-HTP and PMA was blocked by methysergide (Bieger et al, 1972;Menon et al, 1976), indicating that the 5-hydroxytryptaminergic system is involved, the increase of MTA induced by 5-HTP was not blocked but slightly potentiated by chlorimipramine. Thus 5-HTP activates MTA by increasing the availability of 5-HT and its effect is potentiated by chlorimipramine which blocks the reuptake of 5-HT.…”

Section: Discussionmentioning

confidence: 99%

5‐HYDROXYTRYPTAMINE UPTAKE INHIBITORS BLOCK para‐METHOXYAMPHETAMINE‐INDUCED 5‐HT RELEASE

Tseng

1979

British J Pharmacology

View full text Add to dashboard Cite

I Activation of myoclonic twitch activity (MTA) of suprahyoideal muscle after p-methoxyamphetamine (PMA) administration in rats anaesthetized with urethane has previously been reported to be due to brain 5-hydroxytryptamine (5-HT) release. Increased MTA caused by PMA was blocked by chlorimipramine (0.1 to 1 mg/kg) and fluoxetine (0.3 to 3 mg/kg) but not by desipramine (3 mg/kg).2 The 5-hydroxytryptophan-induced increase of MTA of suprahyoideal muscle in rats pretreated with pargyline was not blocked by chlorimipramine but was blocked by methysergide.

show abstract

A model for the quantitative study of central dopaminergic and serotoninergic activity

Cited by 63 publications

References 14 publications

Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine receptor”

Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine receptor”

Effects of Drugs Acting on Cerebral 5‐hydroxytryptamine Mechanisms on Dopamine‐dependent Turning Behaviour in Mice

5‐HYDROXYTRYPTAMINE UPTAKE INHIBITORS BLOCK para‐METHOXYAMPHETAMINE‐INDUCED 5‐HT RELEASE

Contact Info

Product

Resources

About