Indirect dopamine agonists augment the locomotor activating effects of the κ-opioid receptor agonist U-50,488 in preweanling rats

• Published in: Developmental psychobiology Vol. 34; no. 3; pp. 183 - 193
• Main Authors: McDougall, Sanders A., Rodarte-Freeman, Audrey L., Nazarian, Arbi
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.04.1999
• Subjects: Age Factors; Amphetamine - pharmacology; Analysis of Variance; Animals; Behavior, Animal - drug effects; Benzofurans - pharmacology; cocaine; Cocaine - pharmacology; dopamine; Dopamine Agonists - pharmacology; Drug Interactions; Female; Locomotion - drug effects; Male; Methylphenidate - pharmacology; NPA; ontogeny; Pyrrolidines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa - agonists; Stereotyped Behavior - drug effects; U-50; U‐50,488; κ-opioid
• ISSN: 0012-1630; 1098-2302
• DOI: 10.1002/(SICI)1098-2302(199904)34:3<183::AID-DEV3>3.0.CO;2-1

κ‐Opioid receptor agonists (e.g., enadoline or U‐50,488) increase the locomotor activity of preweanling rats, while the same drugs depress the locomotor activity of adults. Curiously, direct stimulation of dopamine (DA) D2‐like receptors fully attenuates the U‐50,488‐induced locomotor activity of preweanling rats. The purpose of the present study was to determine whether indirect DA agonists (i.e., cocaine, methylphenidate, and amphetamine) would also attenuate U‐50,488's behavioral effects. In two experiments, 17‐day‐old rats were injected with saline or U‐50,488 (5 mg/kg, sc) and locomotor activity and stereotyped sniffing were assessed. After 20 min, the saline‐ and U‐50,488‐pretreated rats were injected with saline, cocaine (5, 10, or 20 mg/kg, ip), methylphenidate (10 or 20 mg/kg, ip), amphetamine (2.5 or 5 mg/kg, ip), or the direct D2‐like receptor agonist NPA (1 mg/kg, ip). As expected, U‐50,488 dramatically enhanced the locomotor activity of 17‐day‐old rats, while attenuating the stereotyped sniffing caused by indirect and direct DA agonists. All three indirect DA agonists augmented U‐50,488's locomotor activating effects across the initial 10 min of testing and then activity declined to U‐50,488 control values. Direct stimulation of DA receptors produced nearly opposite effects because NPA attenuated U‐50,488‐induced locomotor activity across the entire testing session. It is uncertain why direct and indirect DA agonists affected U‐50,488‐induced locomotor activity differently, but the relative amount of DA D1‐like receptor activation is probably not responsible. © 1999 John Wiley & Sons, Inc. Dev Psychobiol 34: 183–193, 1999