Modification of morphine-induced analgesia, tolerance and dependence by bromocriptine.
The effect of two doses of bromocriptine, a dopamine agonist, on morphine-induced analgesia, tolerance and dependence was investigated in mice. Bromocriptine at doses of 0.04 and 0.08 mg/kg did not affect the baseline tail flick latency of mice but potentiated the morphine analgesia. Pretreatment of mice with 5 mg/kg of sulpiride, a D-2 antagonist, not only blocked the effect of 0.08 mg/kg of bromocriptine but also antagonized the morphine analgesia. Control animals given daily injections of 10 mg/kg of morphine rapidly developed tolerance to the analgesic effect. A combined treatment of bromocriptine with morphine given daily suppressed the development of tolerance to morphine analgesia. However, development of tolerance to morphine analgesia was not significantly modified in the animals treated daily with bromocriptine (0.08 mg/kg) plus sulpiride (5 mg/kg). Acute dependence was induced by the administration of 100 mg/kg of morphine. The administration of bromocriptine 30 min before naloxone significantly decreased the ED50 value for naloxone for inducing jumping in mice. Coadministration of sulpiride and bromocriptine attenuated the ability of bromocriptine to potentiate the withdrawal syndrome of morphine dependence. The results indicate that bromocriptine potentiates morphine analgesia, suppresses the development of tolerance to morphine analgesia but exacerbates opiate withdrawal signs in morphine-dependent mice. These effects of bromocriptine appear to be mediated via D-2 receptors.
Gomaa
A A
AA
Department of Pharmacology, Anaesthesia and Neurology, Faculty of Medicine, Assiut University, Egypt.
Mohamed
L H
LH
Ahmed
H N
HN
D000700:Analgesics; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology
D000700:Analgesics; D011954:Receptors, Dopamine; D009270:Naloxone; D001971:Bromocriptine; D009020:Morphine; D013469:Sulpiride