Cessation of chronic nicotine administration enhances wet-dog shake responses to 5-HT2 receptor stimulation in rats.
BACKGROUND
The involvement of central serotonergic systems has been hypothesized clinically to contribute to nicotine withdrawal symptoms. However, involvement of the serotonin2 (5-HT(2)) receptor system in nicotine withdrawal is not clear.


OBJECTIVE
The changes in wet-dog shake responses induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT(2) receptor agonist, following nicotine cessation was investigated in rats.


METHODS
DOI (1 mg/kg SC) was administered 24 h after the final treatment of saline or nicotine (0.5 mg/kg per day SC) for 7 or 21 days.


RESULTS
Cessation of nicotine administration for 7 or 21 days increased DOI-induced wet-dog shake responses. A single administration of nicotine (0.5 mg/kg SC) had no effect on DOI-induced wet-dog shakes. The enhancement by the cessation of nicotine treatment for 7 days was abolished by coadministration of nicotine. Mecamylamine (3 mg/kg IP), a nicotinic receptor antagonist, precipitated DOI-induced wet-dog shake responses in rats chronically treated with nicotine but not with saline.


CONCLUSIONS
These findings suggest that cessation of chronic nicotine produced increased sensitivity to 5-HT(2) receptor systems, and that the 5-HT(2) receptor systems may be involved in the nicotine withdrawal symptoms.
Suemaru
K
K
Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Araki
H
H
Kitamura
Y
Y
Yasuda
K
K
Gomita
Y
Y
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D000662:Amphetamines; D018722:Nicotinic Agonists; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D009538:Nicotine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine