Alpha 2-adrenoceptor modulates the release of acetylcholine from the rostral ventrolateral medulla in response to morphine.
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.
Pharmacy Practice and Research Center, Showa Pharmaceutical University, Higashitamagawagakuen, Machida, Tokyo, Japan.
Kazuki
K
Kushida
Kota
K
Ishida
Jun
J
Kikuta
Masatoshi
M
Kato
Toshimitsu
T
Uchiyama
Kyoji
K
Taguchi
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
D018341:Receptors, Adrenergic, alpha-2; D009020:Morphine; D000109:Acetylcholine