mise à jour du
18 mars 2004
Act Neurobiol Exp
1996; 56; 15-19
 Nitric oxide (NO) and central dopamine (DA) D3 receptor reactivity to quinpirole in rats
R Brus , R Szkilnik, RM Kostrzewa
Departrnent of Pharmacology, Silesian Academy of Medicine, Zabrze, Poland
Department of Pharmacology, College of Medicine, East Tennessee State University, Johnson City, USA


Introduction : Recent evidence suggest that nitric oxide (NO), a potent activator of the guanyl-cyclase-cyclic GMP enzyme system in the brain and in peripheral tissues, acts as a novel intracellular messenger of the central nervous system (CNS). It has been suggested that in the CNS, NO is implicated with physiological function such a memory and learning, regulation of cerebrovascular flow, food and water intake and mediation of nociception). It has also been involved in the neurotoxicity of Alzheimer's and Huntington's diseases, in cerebral ischemia and stroke, in alcohol - induced brain damage, and in the release and uptake of neurotransmitters in mammalian brain.
Because central DA systems are known to be involved in the many physiological and pathological activities in mammals and in the human the aim of this study was to examine the role of NO-synthase inhibitor and NO-donor on the reactivity of the central DA D3 receptor reactivity to agonist. For this reason we have been used specific behavioural procedure such yawning behaviour. [...]
Discussion : Central DA agonists are known to induce yawning behaviour in male rats. Because D3 receptors have 113-fold great affinity for quinpirole as compare to D2, and because low doses of quinpirole induced yawning behaviour, it has been postulated that D3 receptor is responsible for DA agonist - induced yawning behaviour. Recently, we found that ontogenie treatments with the DA agonist quinpirole would sensitize receptors to quinpirole - induced yawning responses in adulthood, and in present experiment we have confirm previous finding.
NO is also known to inhibit DA release in the striatum of rats, but on the other hand it does not affect amphetamine - stimulated DA release in nucleus accumbens and inhibits DA uptake in rat striatal synaptosomes. Some authors have shown that NO is capable of inducing DA release from striatal slices. On the behavioural level it has been shown that NO participates in yawning behaviour of rats after apomorphine challenge. Peripheral and central administration of NAME and NMMA (N-monomethyl-L-arginine), the inhibitors of NO synthase prevents apomorphine - induced yawning. We have confirm above results using more specific D3 agonist - quinpirole. Beside we have shown that exogenous NO donor L-ARGININE does not influenced reactivity of the central D3 receptor in rats.
In conclusion, our results suggest that NO play important modulatory role as an agent of the central DA D3 receptor activity.
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