Indirect dopamine agonists augment the locomotor activating effects of the κ-opioid receptor agonist U-50,488 in preweanling rats
✍ Scribed by Sanders A. McDougall; Audrey L. Rodarte-Freeman; Arbi Nazarian
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 144 KB
- Volume
- 34
- Category
- Article
- ISSN
- 0012-1630
No coin nor oath required. For personal study only.
✦ Synopsis
Opioid receptor agonists (e.g.,488)
increase the locomotor activity of preweanling rats, while the same drugs depress the locomotor activity of adults. Curiously, direct stimulation of dopamine (DA) D 2 -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 D 2 -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-50,488induced locomotor activity differently, but the relative amount of DA D 1 -like receptor activation is probably not responsible.