ROLE OF DOPAMINE-RECEPTORS IN THE DUAL EFFECT OF NALOXONE ON QUINPIROLE-INDUCED YAWNING IN MORPHINE PRETREATED RATS

The present study was undertaken to determine the state of sensitivity of dopamine D2/D3 receptors involved in the mediation of yawning beha viour at various times following acute morphine administration to rats . Morphine (3.0 mg/kg, sc.) induced a biphasic effect on locomotor act ivity: an initial inhibitory phase lasting for about 30 min was after about an hour followed by a phase of locomotor activation lasting for about 60 min. Dopamine D2/D3 receptor agonist quinpirole (0.01-0.1 mg/ kg, sc.) induced yawning behaviour in rats. Morphine given at 15 or 60 min before (inhibitory phase) inhibited the yawning response to quinp irole (0.1 mg/kg) but not when given at 90 or 120 min before (stimulat ory phase). Naloxone (1.0 mg/kg) given 10 min before quinpirole restor ed yawning inhibited by morphine pretreatment during the inhibitory ph ase (15-60 min after morphine). However, during the morphine-induced s timulatory phase naloxone strongly inhibited the yawning response to q uinpirole. D1 receptor antagonist SCH 23390 -tetrahydro-3-methyl-5-phe nyl-1H-3-benzazepin-7-ol hemimaleate] at 0.01 mg/kg did not affect qui npirole-induced yawning or its inhibition by morphine, However, in rat s which received morphine 90 min prior to testing yawning, SCH 23390 e nhanced quinpirole-induced yawning behaviour as compared with morphine - or saline-pretreated animals. The data obtained in the present study indicate that morphine pretreatment initially induces a lack of respo nsiveness of the D2/D3 receptors mediating yawning behaviour and subse quently increases their sensitivity. However, the behavioural expressi on of hypersensitivity of these receptors seems to be attenuated by th e concomitant activation of D1 receptors after morphine pretreatment, and thus the enhanced response to quinpirole is first seen after block ade of D1 receptors.