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.

Loss of locomotor sensitisation in response to morphine in D1 receptor deficient mice

“…The D1 antagonist SCH 23 390 was reported to enhance morphine analgesia in the hot-plate test (Kiritsky-Roy et al 1989) and tail immersion test (Rooney and Sewell 1989), findings which are in agreement with the results of the present study. Other studies have suggested a link between the dopaminergic systems in a way that dopamine exerts an inhibitory effect on pathways sensitive to opioids (Ohno et al 1987).…”

Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not

“…With respect to raclopride (Hoffman and Donovan 1995) catalepsy was obtained at 0.5 mg/kg, whereas our data indicated cataleptic effects near 0.2 mg/kg. Minimal cataleptic effects (3-cm cork test) of eticlopride have been reported at 0.15 mg/kg (Kiritsy-Roy et al 1989). Therefore, the doses of D 2 antagonists that induced microcatalepsy in the operant setting were at or below the lower end of the dose ranges reported to induce conventional catalepsy.…”

The dopamine D3/2 agonist 7-OH-DPAT attenuates the development of morphine tolerance but not physical dependence in rats

“…Indeed, D1 and D2 agonists and antagonists have been shown to attenuate, enhance, and have no effect on the acute antinociceptive effects of mu agonists (Cook et al 1999;Kiritsy-Roy et al 1989;McGilliard and Takemori 1979;Morgan and Franklin 1991;Rooney and Sewell 1989). One goal of the present study was to determine if 7-OH-DPAT can modulate the effects of mu agonists under chronic conditions.…”

“…phine and other mu agonists (see, for example, Cook and Picker 1998;Cook et al 1999;Kiritsy-Roy et al 1989;McCarten and Lal 1979;Shippenberg et al 1993). Indeed, D1 and D2 agonists and antagonists have been shown to attenuate, enhance, and have no effect on the acute antinociceptive effects of mu agonists (Cook et al 1999;Kiritsy-Roy et al 1989;McGilliard and Takemori 1979;Morgan and Franklin 1991;Rooney and Sewell 1989).…”