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, s.c.) 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, s.c.) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Zharkovsky
A
A
Department of Pharmacy, University of Helsinki, Finland.
Moisio
J
J
Kivastik
T
T
Ahtee
L
L
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D011292:Premedication; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015000:Yawning / Q000187:drug effects*
D001552:Benzazepines; D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D009270:Naloxone; D009020:Morphine