Enhanced quinpirole response in rats lesioned neonatally with 5,7-dihydroxytryptamine.
The ontogenic destruction of dopamine (DA) neurons in rat brain is associated with supersensitization of DA D1 receptors. This effect is attenuated when rats are cotreated in ontogeny with the serotonin (5-HT) neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). In an attempt to determine whether 5-HT fibers might have a similar modulatory role on the sensitivity of the DA D2 receptor complex, we pretreated rats with desipramine HCl (20 mg/kg, IP, base), 1 h before the DA neurotoxin, 6-hydroxydopamine (6-OHDA; 134 micrograms ICV, base) and/or 5,7-DHT (75 micrograms ICV) and/or vehicle. At about 3 months after birth dose-effect curves for quinpirole-induced oral activity were constructed for each group of rats. We found that quinpirole, an agonist for the DA D2 receptor complex, produced a dose-related increase in oral activity in all groups of rats. After a 200 micrograms/kg dose of quinpirole HCl, however, neonatal 5,7-DHT-lesioned rats had a peak oral response of 54.4 +/- 5.1 (mean and SEM) vs. 22.6 +/- 4.8 for control rats (p < 0.01). In neonatal 6-OHDA-lesioned rats this dose of quinpirole increased oral activity to 36.8 +/- 5.8 oral movements (p < 0.05 vs. control). In rats lesioned with both 5,7-DHT and 6-OHDA, the oral response was not different from control. The enhanced oral response to quinpirole in 5,7-DHT-lesioned rats was attenuated by spiperone, an antagonist for the DA D2 receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)
Brus
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Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA.
Plech
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Kostrzewa
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RM
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004357:Drug Synergism; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D016627:Oxidopamine; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*
D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D019257:Quinpirole; D015116:5,7-Dihydroxytryptamine; D016627:Oxidopamine