Influence of morphine and dopamine receptor sensitization on locomotor activity in mice.
In the present study, the influence of morphine- and dopamine receptor antagonists-induced sensitization on morphine-induced locomotion in mice was investigated. Morphine (30, 40 and 50 mg/kg) increased, while lower doses of the opioid (10 and 20 mg/kg) decreased locomotor activity of mice. Subchronic repeated pretreatment of animals with morphine showed an increase in locomotion induced by the opioid. Clozapine reduced locomotor activity induced by morphine in both the naïve and subchronic morphine-treated animals. Subchronic pretreatment of clozapine also caused an increase in the locomotion induced by morphine. Sulpiride also decreased locomotion induced by morphine and its subchronic administration of the drug caused an increase in morphine- or apomorphine-induced locomotion. Co-administration of clozapine with sulpiride did not elicit potentiation in inhibiting the morphine effect. The D2 receptor mRNA expression was also increased by repeated morphine administration. It may be concluded that morphine-induced sensitization may be due to increase in D2 receptor mRNA expression. Sulpiride and clozapine may induce sensitization and also inhibit morphine-induced locomotion through their dopamine receptor blocking properties.
Heidari
Parviz
P
Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
Sahebgharani
Mousa
M
Riazi
Gholamhossein
G
Zarrindast
Mohammad-Reza
MR
D000818:Animals; D003024:Clozapine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013469:Sulpiride / Q000494:pharmacology
D018492:Dopamine Antagonists; D018756:GABA Antagonists; D011954:Receptors, Dopamine; D017450:Receptors, Opioid, mu; D009020:Morphine; D013469:Sulpiride; D003024:Clozapine