The effects of intraperitoneal administration of antagonists and development of morphine tolerance on the antinociception induced by stimulating the anterior pretectal nucleus of the rat

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Abstract
1 The effects of intraperitoneal administration of antagonists to morphine, 5-hydroxytryptamine (5-HT), noradrenaline and dopamine have been studied on the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) of the rat. 2 A 15 s period of 35 μA sine wave stimulation of APtN significantly increased the latency of the tail flick reflex to noxious heat for periods up to 1 h. 3 Naloxone (0.25-1.0 mg kg−1) attenuated the effects of APtN stimulation in a dose-dependent manner. In rats made tolerant to morphine by daily administration of morphine, the antinociceptive effects of APtN stimulation were significantly reduced. 4 The 5-HT receptor antagonists methysergide (5 mg kg−1) and ketanserin (1 mg kg−1), the dopamine receptor antagonist haloperidol (1 mg kg−1) and the β-adrenoceptor antagonist propranolol (1 mg kg−1) had little effect on the antinociceptive effects of stimulating the APtN. 5 α-Adrenoceptor antagonists caused a dose-dependent antagonism of the response. The order of potency was; idazoxan > prazosin > phenoxybenzamine, the respective ED50 for each drug being 0.08: 0.45: 1.5 mg kg−1. 6 It is concluded that antagonism at opioid receptors and α-adrenoceptors but not β-adrenoceptors, dopamine or 5-HT receptors reduces the antinociceptive effects of APtN stimulation. This differs from the reported effects of these antagonists on the antinociception caused by stimulating other sites in the brain.