DSP-4 prevents dopamine receptor priming by quinpirole

• Published in: Pharmacology, biochemistry and behavior Vol. 84; no. 1; pp. 3 - 7
• Main Authors: Nowak, PrzemysŁaw, Labus, Łukasz, Kostrzewa, Richard M., Brus, Ryszard
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2006; Elsevier Science
• Subjects: Animals; Behavior, Animal - drug effects; Benzylamines - pharmacology; Biological and medical sciences; Dopamine; Dopamine receptor; Drug Antagonism; DSP-4; Female; Medical sciences; Pregnancy; Quinpirole; Quinpirole - antagonists & inhibitors; Quinpirole - pharmacology; Rats; Rats, Wistar; Receptor priming; Receptor supersensitivity; Receptors, Dopamine - drug effects; Yawning; Quinpirole; Yawning; Dopamine; Dopamine receptor; Receptor priming; Rats; Receptor supersensitivity; DSP-4; Agonist; Rat; Priming effect; Rodentia; Cognition; Catecholamine; Prevention; Vertebrata; Mammalia; Diarrhetic shellfish poisoning; Animal; Dopamine agonist; Neurotransmitter; Biological receptor
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2006.03.024

Repeated treatments of rats with the dopamine (DA) D 2 receptor agonist quinpirole, consistently produce long-lived DA D 2 receptor supersensitization, by the process that has been termed priming. Rats so-primed in ontogeny behaviorally demonstrate adulthood enhancement of low-dose quinpirole-induced yawning. Because 1) dopaminergic neurons originate in midbrain nuclei (substantia nigra and ventral tegmental area), and 2) noradrenergic neurons originate in pontine (locus coeruleus) and medullary areas, it might be presumed that these two monoaminergic systems are independent, not interdependent. However, in the present study we demonstrate that there was an attenuation of quinpirole-enhanced yawning at 8 weeks in rats that were 1) primed by repeated neonatal quinpirole HCl treatments (50 μg/kg per day SC) during the first ten days of postnatal ontogeny, and 2) lesioned at 3 days after birth with DSP-4 ( N-2-chloroethyl- N-ethyl-2-bromobenzylamine hydrochloride, 50 mg/kg SC). Dose–effect curves indicated a 23–45% reduction in yawning by DSP-4 treatment of quinpirole-primed rats, acutely treated as adults with quinpirole (25, 50, or 100 μg/kg). Effectiveness of DSP-4 is reflected by the 95% and 99% reductions in norepinephrine contents of frontal cortex and hippocampus, respectively (HPLC/ED method). The findings are supportive of a modulatory role of noradrenergic fibers on dopamine receptor priming (supersensitization) in rat brain.