title: Dopamine D-1 and D-2 receptor antagonists potentiate analgesic and motor effects of morphine.
abstract: To examine the role of dopamine receptor subtypes mediating analgesic and motor responses to opioids, rats were pretreated with either saline or a selective D-1 or D-2 dopamine receptor antagonist 10 min prior to morphine (12 mg/kg IP). Analgesic response latency was determined using the hot plate test (52.5 degrees C and 55 degrees C), and catalepsy was assessed using the abnormal posture test. Morphine increased analgesic response latency to 44.5 +/- 7.9% of the maximum possible response, but had no cataleptic effect in the abnormal posture test. Pretreatment with either the D-1 antagonist, SCH 23390 (50-100 micrograms/kg), or the D-2 antagonist, eticlopride (20-150 micrograms/kg), potently enhanced morphine analgesia as measured on the 52.5 degrees C hot plate. Peak analgesic responses to morphine increased to 100 +/- 0% and 91.9 +/- 7.5% of maximum with the highest doses of SCH 23390 and eticlopride, respectively. These treatments also produced catalepsy. Increasing the hot plate temperature to 55 degrees C reduced response latency in groups treated with either dopamine receptor antagonist plus morphine. This indicates that the animals were capable of responding at a shorter latency and demonstrates that motor impairment cannot account for potentiation of morphine analgesia by D-1 and D-2 antagonists at 52.5 degrees C. These results show that the relationship between dopamine and opioids with respect to analgesic and motor systems involves both dopamine receptor subtypes.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor 48109.
authors.forename: J A
authors.initials: JA
authors.lastname: Kiritsy-Roy
authors.forename: S M
authors.initials: SM
authors.lastname: Standish
authors.forename: L C
authors.initials: LC
authors.lastname: Terry
mesh_terms: D000700:Analgesics; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology
chemical_list: D000700:Analgesics; D001552:Benzazepines; D011954:Receptors, Dopamine; D012457:Salicylamides; D009020:Morphine; C045989:eticlopride