Ontogenetic quinpirole treatments fail to prime for D2 agonist-enhancement of locomotor activity in 6-hydroxydopamine-lesioned rats.
Repeated treatments with a dopamine (DA) D2 receptor agonist results in the induction of DA D2 receptor supersensitivity, as evidenced by enhanced behavioral responses to subsequent D2 agonist treatments - a phenomenon known as priming of receptors. Priming of D2 receptors has been well-studied in otherwise intact (non-lesioned) rats. In contrast to D2 priming, repeated treatments with a DA D1 agonist are unable to prime D1 receptors unless nigrostriatal DA fibers are largely destroyed in early postnatal ontogeny. In order to determine if D2 receptors could be primed in rats in which nigrostriatal DA fibers were largely destroyed in early postnatal ontogeny, rats were (a) lesioned at 3 days after birth with 6-hydroxydopamine (67 micrograms in each lateral ventricle; desipramine, 20 mg/kg IP, 1 h; 6-OHDA), (b) treated daily for the first 28 days after birth with the D2 agonist quinpirole HCl (3.0 mg/kg IP), and (c) observed in adulthood for both quinpirole-induced and SKF 38393- (D1 agonist-) induced locomotor activity and stereotyped activities. In 6-OHDA-lesioned rats in which endogenous striatal DA was reduced by 99%, quinpirole did not produce enhanced locomotor or stereotyped activities. However, SKF 38393 produced increased locomotor and stereotyped activities even after the first dose of SKF 38393. These findings demonstrate that D2 receptors are not primed by ontogenetic quinpirole treatments of neonatally 6-OHDA-lesioned rats, although D2 agonist treatments do at least partially prime D1 receptors in the 6-OHDA-lesioned rats.
Brus
Ryszard
R
Department of Pharmacology, Medical University of Silesia, 41-808 Zabrze, Poland.
Kostrzewa
Richard M
RM
Nowak
Przemysław
P
Perry
Ken W
KW
Kostrzewa
John P
JP
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D003714:Denervation; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity*; D011247:Pregnancy; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013239:Stereotyped Behavior / Q000187:drug effects; D013565:Sympatholytics / Q000633:toxicity*
D015306:Biogenic Monoamines; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine