Evidence for dopamine receptors mediating sedation in the mouse brain

Chiara, G. Di; Porceddu, M.L.; Vargiu, L; Argiolas, Antonio; Gl, Gessa

doi:10.1038/264564a0

Cited by 418 publications

(87 citation statements)

References 15 publications

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“…It had been noted that the acute depressive effects of dopamine agonists are associated with a decline in extracellular levels of dopamine (Di Chiara et al, 1976, 1978, suggesting that a shut-down of dopamine activity may mediate behavioral suppression. The mode of action by which a dopamine agonist could produce this shut-down includes stimulation of somatodendritic D2 autoreceptors to reduce dopamine cell firing (Skirboll et al, 1979), stimulation of D2 autoreceptors on presynaptic terminals to inhibit dopamine release (Rouge-Pont et al, 2002), or both.…”

Section: A Model Of Qnp Sensitizationmentioning

confidence: 99%

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

Perreault

Graham

Bisnaire

et al. 2005

Neuropsychopharmacol

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To assess whether the development and expression of behavioral sensitization to the dopamine D2/D3 agonist quinpirole (QNP) is influenced by coadministration of the kappa opioid receptor agonist U69593, rats received every 3-4 days for a total of 10 treatments an injection of U69593 (0.3 mg/kg) together with an injection of either a postsynaptic (0.5 mg/kg) or a presynaptic dose of QNP (0.05 mg/ kg); locomotor activity was measured after each treatment. Control rats were injected as appropriate with QNP, U69593, and vehicle/ saline. Following chronic treatment, dose-response profiles to QNP were obtained to assess the expression of sensitization; the effect of U69593 on locomotor activity in animals already sensitized to QNP was also assessed. Results showed that cotreatment of U69593 with a postsynaptic dose of QNP doubled the speed and magnitude of sensitization to QNP, while U69593 cotreatment with a presynaptic dose of QNP switched the effects of QNP from locomotor depression to locomotor sensitization. However, U69593 cotreatment with a presynaptic dose of QNP changed a different set of measures of sensitization than did cotreatment with a postsynaptic dose of the dopamine agonist. Together, findings suggest that sensitization to QNP is not a unitary phenomenon but has components that are relatively independent, mediated by distinct pre-and postsynaptic mechanisms and modulated by kappa receptor activity.

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Section: A Model Of Qnp Sensitizationmentioning

confidence: 99%

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

Perreault

Graham

Bisnaire

et al. 2005

Neuropsychopharmacol

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“…The attenuated potency of a low dose of apomorphine (0.05 mg/kg), which is believed to act mainly via presynaptic dopamine D-2 receptors [39), can be explained by a reduced sensitivity of presynaptic D-2 receptors following toluene exposure. This possibility is supported by the increase in the K 0 value of the D-2 agonist binding sites induced Sy toluene (20,21).…”

Section: Areamentioning

confidence: 99%

Subacute exposure to low concentrations of toluene affects dopamine-mediated locomotor activity in the rat

et al. 1991

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SummaryThe effects of low concentrations of toluene (4~80 ppm. 3 days. 6 h/day) were investigated on spontaneous and on apomorphine-induced locomotor activity in the rat. and were correlated to effects on S(-) [N-propyl-3 H(N)]-propylnorapomorphine ([ 3 H]NPA) binding in rat neostriatal membranes. on membrane fluidity. membrane leakage. and calcium levels in synaptosomes from the frontoparietal cortex, the neostriatum and the subcortical limbic area. and on serum hormone levels. Toluene exposure (80 ppm, post-exposure delay 18 h) alone did not affect locomotor activity, but attenuated apomorphineinduced (0.05 mg/kg, s.c.) suppression of rearing. and potentiated apomorphine-induced (I mg/kg. s.c.) increases in locomotion and rearing. Toluene exposure increased the K 0 value of [3H]NPA binding without affecting the Bmax· All these effects were absent at 40 ppm of toluene or at a post-exposure delay of 42 h. Toluene exposure (80 ppm. post-exposure delay of 18 h) did not affect the serum levels of prolactin. TSH, corticosterone. or aldosterone, or synaptosomal membrane fluidity and calcium levels. whereas membrane leakage was increased in the neostriatum. The present study indicates that the reduction of D-2 receptor affinity by short-term. low-dose toluene exposure is accompanied by a reduced D-2 autoreceptor function and an enhanced postsynaptic D-2 receptor function.

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“…Stimulation of presynaptic dopamine receptors, located on the dendrites, soma or axonal terminals of dopamine neurones within the central nervous system, results in suppression of locomotion in rodents (Di Chiara et al, 1976;Strombom, 1976). Suppression of locomotion does not define the mechanism of drug action because this behaviour can be reduced by a range of drugs acting via mechanisms other than stimulation of presynaptic dopamine receptors (eg.…”

Section: Introductionmentioning

confidence: 99%

Dopamine autoreceptors and the effects of drugs on locomotion and dopamine synthesis

Brown

Campbell

Mitchell

et al. 1985

British J Pharmacology

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were examined, together with the relationship between inhibition of locomotion and dopamine synthesis. 2 ED50 potencies to inhibit locomotion of mice were established for drugs from a number of categories. Spiperone 0.02mgkg-' significantly (P<0.05) reversed inhibition of locomotion by known dopamine agonists but not that by the other types of drug. Idazoxan antagonized inhibition of locomotion due to a2-agonists but not dopamine agonists. RU 24926 (N-propyl-N,N-di[2-(3-hydroxyphenyl)ethyl]amine) was antagonized by both spiperone and idazoxan. 3 Only for dopamine agonists was there good correlation (r = 0.97) between potencies to inhibit locomotion in mice and L-dihydroxyphenylalanine (L-DOPA) accumulation in the nucleus accumbens of rats treated with y-butyrolactone and 3-hydroxybenzylhydrazine. The specific dopamine Dragonist, SK&F 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1 -phenyl-H-3-benzazepine), was inactive in both tests at doses up to 10mg kg-'. The mixed dopamine agonist/antagonist, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine, commonly known as (-)-3-PPP, acted as a dopamine agonist in both tests but inhibited locomotion more potently than L-DOPA accumulation. 4 The inhibitory effects of dopamine agonists on locomotion were not prevented by a-methyl-ptyrosine pretreatment. 5 The data suggest that spiperone-reversible inhibition of locomotion in mice is a good criterion for dopamine autoreceptor agonists. The receptors involved are affected by low doses of both dopamine agonists and antagonists and seem similar to those involved in the autoreceptor mediated inhibition of dopamine synthesis. However, inhibition of locomotion is not due simply to suppression of dopamine release brought about as a secondary consequence of effects on synthesis; a separate mechanism for inhibiting dopamine release is probably involved.

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Evidence for dopamine receptors mediating sedation in the mouse brain

Cited by 418 publications

References 15 publications

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

Subacute exposure to low concentrations of toluene affects dopamine-mediated locomotor activity in the rat

Dopamine autoreceptors and the effects of drugs on locomotion and dopamine synthesis

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