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Analgesic effect of the direct D 2 dopamine receptor agonist RU 24926 and cross tolerance with morphine
Author(s) -
Suaudeau C.,
Costentin J.
Publication year - 1995
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1995.tb00274.x
Subject(s) - analgesic , morphine , agonist , (+) naloxone , antagonist , dopamine receptor , pharmacology , chemistry , opioid , dopamine , haloperidol , medicine , endocrinology , receptor
Summary— The direct D 2 dopamine receptor agonist RU 24926, administered subcutaneously to mice, elicited, starting at the dose of 0.125 mg/kg, a dose dependent analgesic effect, assessed as the jump latency from a hot plate (55°C). The analgesic effect induced by 0.25 mg/kg RU 24926 was dose dependently antagonized by the preferential D 2 dopamine receptor antagonist haloperidol (ID 50 = 15.1 ± 3.3 μg/kg sc) as well as by the opioid receptor antagonist naloxone (ID 50 = 0.59 ± 0.17 mg/kg sc). The reversion of RU 24926‐induced analgesia by naloxone was not accompanied by a reversion of hypothermia. Semi‐chronic administration of RU 24926 (2.5 mg/kg, sc, 3 times a day for 3 days) completely desensitized to the analgesic effect induced by a 0.25 mg/kg test dose of RU 24926 and partially reduced the analgesic effect of low doses of morphine (0.5, 1, 1.5 mg/kg). Conversely, semi‐chronic administration of morphine (32 mg/kg sc, twice daily for 4 days) completely desensitized the analgesic effect induced by a 2 mg/kg test dose of morphine and partially reduced the analgesic effect of RU 24926 (0.25, 0.5 and 1 mg/kg). The RU 24926‐induced analgesia did not seem to be the nonspecific consequence of its hypothermic effect since: i) the time course of hypothermia was shorter than that of analgesia, ii) the analgesic effect was observed in inbred C3H mice which have a low sensitivity to the hypothermic effect of direct agonists of D 2 dopamine receptors and iii) in mice semi‐chronically treated with morphine and thereby made tolerant to the RU 24926‐induced analgesia, the hypothermic effect of RU 24926 was found unchanged. It is suggested that the stimulation of D 2 dopamine receptors, without obvious link with the resultant hypothermia, releases an opioid material which induces analgesia.