Alpha 2-adrenoceptor mediated inhibition of [3H]dopamine release from nucleus accumbens slices and monoamine levels in a rat model for attention-deficit hyperactivity disorder.
The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention-deficit hyperactivity disorder (ADHD). The behavioural problems have been suggested to be secondary to altered reinforcement mechanisms in which nucleus accumbens dopaminergic activity plays an important role. Interaction between the noradrenergic and dopaminergic system in the nucleus accumbens has been implicated in the locomotor hyperactivity and impaired discriminative performance of SHR. The present study therefore investigated whether there was any change in the alpha 2-adrenoceptor mediated inhibition of dopamine release from nucleus accumbens slices of SHR in comparison with their normotensive Wistar-Kyoto (WKY) controls. The electrically stimulated release of [3H]dopamine (DA) from nucleus accumbens slices was decreased to a similar extent by UK14,304, an alpha 2-adrenoceptor agonist, in SHR and WKY. Basal norepinephrine (NE) levels were increased in locus coeruleus (LC) and A2 noradrenergic nuclei, but not in the A1 nucleus of SHR, while basal serotonin (5-HT) levels were increased in all these pons-medulla nuclei. These results suggest that a primarily dysfunctional LC and A2 nucleus does not have a secondary effect on dopaminergic transmission in the nucleus accumbens via alpha 2-adrenoceptor mediated inhibition of DA release. Basal monoamine levels in several brain areas of SHR were significantly different from that of WKY. DA, and 5-HT turnover were decreased in SHR versus WKY suggesting hypofunctional dopaminergic and serotonergic systems in some brain areas of SHR.
de Villiers
A S
AS
Department of Chemical Pathology, University of Stellenbosch, Tygerberg Hospital, Republic of South Africa.
Russell
V A
VA
Sagvolden
T
T
Searson
A
A
Jaffer
A
A
Taljaard
J J
JJ
D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism*; D015306:Biogenic Monoamines / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D014316:Tritium
D058647:Adrenergic alpha-2 Receptor Agonists; D000959:Antihypertensive Agents; D015306:Biogenic Monoamines; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; D000068438:Brimonidine Tartrate; D004298:Dopamine; D009638:Norepinephrine