Discriminative-stimulus effects of morphine in combination with alpha- and beta-noradrenergic agonists and...

Studies have shown that the noradrenergic system is involved in the analgesic effects of opioids and in the expression and development of physical signs of opioid withdrawal. The purpose of the present experiment was to determine if the noradrenergic system was involved in the discriminative effects of morphine in rats trained to discriminate 5.6 mg/kg morphine from saline under a fixed-ratio schedule of food presentation. A range of doses of morphine (0.3-10.0 mg/kg) produced dose-dependent increases in morphine-appropriate responding without substantial decreases in response rate. Several experiments were conducted to determine whether a number of noradrenergic agonists and antagonists 1) substitute for morphine or 2) alter the discriminative-stimulus effects of morphine when administered concurrently. The alpha 2 agonist clonidine (0.003-0.1 mg/kg), the alpha 1 antagonist prazosin (0.1-10.0 mg/kg), the alpha 2 antagonist yohimbine (0.1-10.0 mg/kg), the beta 2 agonist salbutamol (0.03-10.0 mg/kg), and the beta antagonist propranolol (1.0-10.0 mg/kg), neither substituted for morphine nor altered the discriminative-stimulus effects of morphine when administered in combination. These data suggest that the noradrenergic system is not involved in the discriminative-stimulus effects of 5.6 mg/kg morphine in rats.