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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