Role of central nicotinic and beta-adrenergic receptors in the onset and further development of tail-tremor induced by repeated nicotine administration to rats.
The effects of nicotinic and beta-adrenergic receptor antagonists on tail-tremor induced by repeated nicotine administration were investigated in rats. The daily administration of nicotine (0.5 mg/kg/day, s.c.) for 8 days resulted in an augmentation of tail-tremor. However, repeated administration of dimethyl phenyl piperazinium iodide (1 mg/kg/day, s.c.) for 8 days did not cause tail-tremor. Mecamylamine (0.5 mg/kg, i.p), administered before the nicotine injection on each day, abolished the tail-tremor. After discontinuation of the mecamylamine treatment, nicotine injections caused tail-tremor augmentation. Propranolol (20 mg/kg, i.p.), administered before the nicotine on each day, suppressed the appearance of tail-tremor. After the discontinuation of propranolol treatment, the degree of tail-tremor induced by a single injection of nicotine on day 9 was much greater in the propranolol-treated group than in the saline-treated control group. Neither carteolol (20 mg/kg, i.p.) nor metoprolol (20 mg/kg, i.p.) treatment showed such effects. Intraspinal injection of 6-hydroxydopamine markedly enhanced the tail-tremor induced on the first day of nicotine injection. This effect became more intense on subsequent administration of nicotine. The enhanced tail-tremor following 6-hydroxydopamine treatment was abolished by mecamylamine (0.5 and 1 mg/kg, i.p.), and was suppressed by propranolol (5-20 mg/kg, s.c.) in a dose-dependent manner. These results suggest that central nicotinic receptors are essential for the onset and for the further development of tail-tremor induced by the repeated administration of nicotine, and that beta 2-adrenoceptors are associated with the tremor mechanism. Moreover, spinal noradrenergic mechanisms may be involved in the manifestation of this phenomenon.
Suemaru
K
K
Division of Pharmacy, Misasa Medical Branch, Okayama University Medical School, Tottori, Japan.
Kawasaki
H
H
Oishi
R
R
Gomita
Y
Y
Tanizaki
Y
Y
D018663:Adrenergic Agents / Q000008:administration & dosage / Q000633:toxicity; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002354:Carteolol / Q000008:administration & dosage / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000633:toxicity*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013623:Tail; D014202:Tremor / Q000139:chemically induced*
D018663:Adrenergic Agents; D000319:Adrenergic beta-Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D018343:Receptors, Adrenergic, beta-2; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide; D008464:Mecamylamine; D009538:Nicotine; D016627:Oxidopamine; D002354:Carteolol; D011433:Propranolol; D008790:Metoprolol