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1 Nociceptive tail flick latencies (TFL) were recorded in response to noxious thermal stimuli applied to lightly anaesthetized rats. The effects of intrathecally administered dopamine receptor agonists alone and combined with dopamine receptor antagonists were examined upon the TFL. Experiments were repeated on animals made supersensitive to dopamine following withdrawal from 28 day administration of haloperidol. 2 In untreated animals the D2-receptor agonist LY 171555 and apomorphine produced an increase in TFL. In contrast, the D1-receptor agonist SKF38393 had no significant effect on TEL. 3 Following haloperidol-induced dopamine-supersensitivity, SKF 38393 produced an increase in TFL. In contrast, LY 171555 and apomorphine had minimal effects on TFL in this preparation. 4 In animals not treated with haloperidol, the dopamine receptor antagonists SCH 23390 and (± )-sulpiride both blocked the increase in TFL produced by the D2-agonists. 5 SCH23390 and (±)-sulpiride also blocked the increase in TFL produced by SKF38393 in haloperidol-supersensitized animals. 6 The antinociceptive action of intrathecally administered dopamine agonists appears to be mediated via D2-receptors. Whether the antinociception produced by SKF 38393 is exclusively contingent upon the activation of D1-receptors in the dopamine-supersensitive animal is as yet unresolved.

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The antagonistic effects of the two benzomorphan opioid antagonists, Mr-1452 and Mr-2266 and their respective (+)-isomers Mr-1453 and Mr-2267 upon morphine, ethylketocyclazocine (EKC), D-ala2-D-leu5-enkephalinamide (BW 180-C) and oxotremorine (OTMN) antinociceptive activity in mice were investigated. Pretreatment with either Mr-1452 (2.0 mg Kg-1 i.p.) or Mr-2266 (2.0 mg kg-1 i.p.) significantly antagonized the antinociceptive effects of the three opioid agonists in the hot plate test, but were ineffective against OTMN, which in contrast was antagonized by the (+)-isomers. Interaction between the antagonists and submaximal analgesic doses of the opioids or OTMN produced similar results in the tail immersion assay. However, the effect of Mr-2267 on OTMN was biphasic and this contrasted with Mr-1453 which produced consistent and graded antagonism.