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 behaviour at various times following acute morphine administration to rats. Morphine (3.0 mg/kg, sc.) induced a biphasic effect on locomotor activity: 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 quinpirole (0.1 mg/kg) but not when given at 90 or 120 min before (stimulatory phase). Naloxone (1.0 mg/kg) given 10 min before quinpirole restored yawning inhibited by morphine pretreatment during the inhibitory phase (15-60 min after morphine). However, during the morphine-induced stimulatory phase naloxone strongly inhibited the yawning response to quinpirole. D1 receptor antagonist SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hemimaleate] at 0.01 mg/kg did not affect quinpirole-induced yawning or its inhibition by morphine, However, in rats which received morphine 90 min prior to testing yawning, SCH 23390 enhanced 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 responsiveness of the D2/D3 receptors mediating yawning behaviour and subsequently increases their sensitivity. However, the behavioural expression of hypersensitivity of these receptors seems to be attenuated by the concomitant activation of D1 receptors after morphine pretreatment, and thus the enhanced response to quinpirole is first seen after blockade of D1 receptors.