SEROTONIN INVOLVEMENT IN THE DISCRIMINATIVE STIMULUS EFFECTS OF MU-OPIOIDS AND KAPPA-OPIOIDS IN RATS

The role of serotonin (5-HT) in the discriminative stimulus effects of opioids was examined using a two-lever, food-reinforced drug discrimi nation procedure. The effects of the 5-HT1A full agonist 8-OH-DPAT, th e 5-HT1A partial agonist buspirone and the 5-HT2 antagonist ketanserin were evaluated in fats trained to discriminate the mu opioid agonist morphine, or the kappa opioid agonist U50,488 from saline. In rats tra ined to discriminate 5,6 mg/kg of morphine from saline, morphine dose- dependently substituted (produced greater than or equal to 80% morphin e-appropriate responding) for the morphine stimulus. In contrast, U50, 488, 8-OH-DPAT and ketanserin did not substitute for morphine, and bus pirone produced only a small degree of substitution (approx. 40% morph ine-appropriate responding). When administered in combination with mor phine, 8-OH-DPAT, but not buspirone and ketanserin, attenuated the dis criminative stimulus effects of higher doses of morphine. In rats trai ned to discriminate 5.6 mg/kg of U50,488 from saline, U50,488 dose-dep endently substituted for the U50,488 stimulus. When administered alone , 8-OH-DPAT and buspirone partially substituted (produced between 40% and 79% U50,488-appropriate responding) for the U50,488 stimulus, wher eas morphine and ketanserin did not substitute for U50,488, The opioid antagonist naltrexone failed to antagonize the effects of 8-OH-DPAT a nd buspirone suggesting that the effects of these drugs in U50,488-tra ined rats were not mediated by opioid receptors. When administered in combination with U50,488, 8-OH-DPAT, but not buspirone or ketanserin, attenuated the discriminative stimulus effects of the training dose of U50,488. These results suggest that the 5-HT system is involved in th e discriminative stimulus effects of both morphine and U50,488, althou gh the exact nature of this 5-HT involvement is not clear.