Systemic administration of arecoline reduces ethanol-induced sleeping through activation of central muscarinic receptor in mice.
BACKGROUND
Epidemiological evidence of co-use of alcohol and areca nuts suggests a potential central interaction between arecoline, a major alkaloid of areca and a muscarinic receptor agonist, and ethanol. Moreover, the central cholinergic system plays an important role in the depressant action of ethanol and barbiturates. The purpose of this study was to investigate the effects of arecoline on pentobarbital- and ethanol-induced hypnosis in mice.


METHODS
Male ICR mice were tested for locomotor activity following acute systemic administration of ethanol alone, arecoline alone, or ethanol plus arecoline. For the loss of the righting reflex (LORR) induced by pentobarbital and ethanol, sleep latency and sleeping duration were evaluated in mice treated with arecoline alone or the combination of arecoline and scopolamine or methscopolamine.


RESULTS
Ethanol (1.0 to 3.0 g/kg, i.p.) reduced locomotor activity significantly and a declining trend was observed after treatment with arecoline (0.25 to 1.0 mg/kg, i.p.), but there were no synergistic effects of ethanol and arecoline on locomotor activity. The experiments on LORR demonstrated that arecoline (0.125 to 1.0 mg/kg, s.c.) shortened the duration of sleeping induced by ethanol (4.0 g/kg, i.p.), but not pentobarbital (45 mg/kg, i.p.). In addition, alterations of sleep latency were not obvious in both pentobarbital- and ethanol-induced LORR. Statistical analyses revealed that scopolamine (centrally acting), but not methscopolamine (peripherally acting), could antagonize the effect of arecoline on the duration of ethanol-induced LORR in mice.


CONCLUSIONS
These results suggest that central muscarinic receptor is a pharmacological target for the action of arecoline to modulate ethanol-induced hypnosis.
Sun
Yan-Ping
YP
National Institute on Drug Dependence, Peking University, Beijing, China.
Liu
Qing
Q
Luo
Juan
J
Guo
Ping
P
Chen
Feng
F
Lawrence
Andrew J
AJ
Liang
Jian-Hui
JH
D000818:Animals; D001115:Arecoline / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000008:administration & dosage*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*
D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D000431:Ethanol; D001115:Arecoline