Antinociceptive effect of agonists microinjected into the anterior pretectal nucleus of the rat

Abstract

Electrical stimulation at many sites within the pretectal complex and adjacent structures of the rat dorsomedial thalamus yields antinociception. It is documented that no other site in this region evokes antinociception longer lasting than that obtained by stimulation of the anterior pretectal nucleus (APtN). The effects of agonists injected into different nuclei of the dorsomedial thalamus on the tail-flick reflex of rats in response to noxious heat was examined. All animals were submitted to intracerebral electrical stimulation and microinjection of agonists. It was confirmed that strong and long lasting antinociception followed brief (15 s), low intensity (35 μA rms) stimulation of the APtN. In addition, l-glutamate (3.5 and 7.0 μg), morphine (1.0 and 5.0 μg), and 5-hydroxytryptamine (5-HT; 2.5 and 5.0 μg), but not acetylcholine (5.0 μg), carbachol (2.5 μg), norepinephrine (5.0 μg), or dopamine (5.0 μg), induced dose-dependent antinociception when microinjected into the APtN. The effect of 5-HT was fully depressed by pretreating animals with methysergide (5 mg/kg, i.p.). A survey of the sites from which morphine and 5-HT induce antinociception revealed that in no site of the dorsomedial thalamus did the effect last longer than after microinjection into the APtN. It is concluded that antinociception evoked by stimulation of the APtN depends on the activation of neuronal cell bodies in the nucleus, and that 5-HT and endogenous opioids may play a physiological role as neurotransmitters mediating antinociception in the APtN.