Dopamine D-1 and D-2 receptor antagonists potentiate analgesic and motor effects of morphine.
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.
Kiritsy-Roy
J A
JA
Department of Neurology, University of Michigan, Ann Arbor 48109.
Standish
S M
SM
Terry
L C
LC
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
D000700:Analgesics; D001552:Benzazepines; D011954:Receptors, Dopamine; D012457:Salicylamides; D009020:Morphine; C045989:eticlopride