[show abstract][hide abstract] ABSTRACT: The present study examined the role of the noradrenergic system in the modulation of acetylcholine (ACh) release in the rostral ventrolateral medulla (RVLM) using in vivo microdialysis of morphine. The basal level of ACh was 325.0 +/- 21.1 fmol/20 microl/15 min in the presence of neostigmine (10 microM). Intraperitoneal (i.p.) administration of 5 and 10 mg/kg morphine significantly increased ACh release by the RVLM. This enhancement was reversed by naloxone (1 mg/kg, i.p.). In addition, pretreatment with yohimbine (0.5 mg/kg, i.p.) or prazosin (0.2 mg/kg, i.p.) attenuated the systemic morphine-induced release of ACh in the RVLM. However, propranolol (0.2 mg/kg, i.p.) did not affect the morphine-induced ACh release. The addition of morphine (10(-4) M) to the perfusion medium increased the ACh release by 72.4% of the predrug values. The increased ACh release induced by local application of morphine was attenuated by pretreatment with yohimbine, but not prazosin. These findings suggest that morphine exerts an indirect stimulatory effect on the release of ACh by the RVLM and that the morphine-induced increase in ACh release is modulated by alpha2-adrenoceptors in freely moving rats.
[show abstract][hide abstract] ABSTRACT: Injecting muscarinic receptor agonists into a specific area of the brainstem produces an antinociceptive response. The present study investigates whether direct injections of the cholinergic agonist, carbachol, into the rat nucleus reticularis gigantocellularis (NRGC)/nucleus reticularis gigantocellularis alpha (NRGCalpha) of the rostral ventrolateral medulla evokes antinociception, and then examines the interference action of cholinergic antagonists in rats. Microinjections of carbachol (0.75, 1.5, 3 micro g/site) prolonged hot plate (HP) and tail flick (TF) responses to noxious heat stimuli in a dose-dependent manner. The level of carbachol-induced antinociception during the HP and TF tests reached a maximum at 5-15 min after carbachol administration in all groups. Thereafter, the peak level progressively decreased and reached the baseline by the end of the experiment. Antinociception induced by carbachol at 3 micro g/site was attenuated by the prior administration of the muscarinic receptor antagonist, atropine (200, 500 ng/site). On the other hand, the nicotinic autonomic ganglion blocker, mecamylamine (1, 3 micro g/site), did not affect subsequent carbachol-induced antinociception. These results suggest that the antinociceptive effects induced by a microinjection of carbachol depend on muscarinic, but not nicotinic, mechanisms within the rat NRGC/NRGCalpha.