Muscimol injections in the nucleus raphé dorsalis block the antinociceptive effect of morphine in rats: apparent lack of 5‐hydroxytryptamine involvement in muscimol's effect

Abstract

1The effect of morphine (3 mg kg-1 subcutaneously) on tail flick in the tail immersion test was studied in rats which had received a muscimol (100 ng) injection either in the nucleus raphe dorsalis (DR) or medianus (MR). 2 The levels of 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus and striatum of muscimol-injected animals. 3Muscimol injections in the DR reduced 5-HIAA concentrations in the striatum but not in hippocampus, whereas in animals which had received muscimol in the MR a selective decrease in hippocampal 5-HIAA levels was found. 4 Muscimol injections in the DR blocked the effect of morphine while no effect was seen in animals which had received muscimol in the MR.5 An injection of 5,7-dihydroxytryptamine (6 tig in 3 pl) in the DR did not change the effect of morphine or muscimol. 6 These findings indicate that muscimol-sensitive neurones in the DR, which are probably not 5-hydroxytryptaminergic, are involved in the effect of morphine on tail flick in tail immersion. The muscimol-sensitive neurones involved in this effect of morphine do not seem to exist in the MR.

Differential regulation of 5‐hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats

“…Local application of GABA receptor agonists in the DRN inhibits 5hydroxytryptaminergic neuronal activity and 5-hydroxytryptamine (5-HT) release and metabolism in the forebrain (Hery & Ternaux, 1981;Nishikawa & Scatton, 1983;Romandini & Samanin, 1984;Tao & Auerbach, 1994). These effects are blocked by specific GABA receptor antagonists Romandini & Samanin, 1984). Furthermore, GABA receptor agonists inhibit 5-HT release from cortex and striatal slices (Bowery et al, 1980;Schlicker et al, 1984) consistent with extensive evidence that GABA is a presynaptic modulator substance.…”

“…GABAergic terminals are present (Belin et al, 1979), and make synaptic connection with 5-hydroxytryptaminergic neurones in the dorsal raphe nucleus (DRN) (Wang et al, 1992). Local application of GABA receptor agonists in the DRN inhibits 5-hydroxytryptaminergic neuronal activity ) and 5-hydroxytryptamine (5-HT) release and metabolism in the forebrain (Hery & Ternaux, 1981;Nishikawa & Scatton, 1983;Romandini & Samanin, 1984;Tao & Auerbach, 1994). These effects are blocked by specific GABA receptor antagonists Romandini & Samanin, 1984).…”

Quantitative immunoelectron microscopic colocalization of GABA and enkephalin in the ventrocaudal periaqueductal gray of the rat

“…Our data is consistent with such a model. Microinjection of GABA antagonists in the PAG produces an antinociception effect (Depaulis et al, 1987) which is reversed by microinjection of the GABA agonist, muscimol (Romandini and Samanin, 1984). Furthermore, since antinociception produced by microinjection of morphine in the PAG can be antagonized by GABA agonists (Depaulis et al, 1987;Moreau and Fields, 1986), a relevant opiate circuitry may also be located in the PAG.…”

Differential modulation by muscimol and baclofen on antinociception induced by morphine, ?-endorphin, d-Pen2,5-enkephalin and U50,488H administered intracerebroventricularly in the mouse

“…Systemic administration of GABAergic agents enhances the antinociception induced by opioids (reviewed by Sawynok 1984Sawynok , 1987Sivam and Ho 1985), although a central administration (intracerebroventricular, i.c.v. ) or direct microinjection into the periaqueductal gray or dorsal raphe nucleus paradoxically reduces morphine-induced antinociception (Romandini and Samanin 1984;Zambotti et al 1982;Zonta et al 1981). Furthermore, GABAergic agents themselves produce antinociception (reviewed by Sawynok 1984Sawynok , 1987Sivam and Ho 1985).…”