Indirect dopamine agonists augment the locomotor activating effects of the kappa-opioid receptor agonist U-50,488 in preweanling rats.
kappa-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, i.p.), methylphenidate (10 or 20 mg/kg, i.p.), amphetamine (2.5 or 5 mg/kg, i.p.), or the direct D2-like receptor agonist NPA (1 mg/kg, i.p.). 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.
McDougall
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SA
Department of Psychology, California State University, San Bernardino 92407, USA.
Rodarte-Freeman
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AL
Nazarian
A
A
D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013239:Stereotyped Behavior / Q000187:drug effects
D001572:Benzofurans; D018491:Dopamine Agonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D008774:Methylphenidate; D000661:Amphetamine; D003042:Cocaine; C067110:enadoline