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Cessation of chronic nicotine administration enhances wet-dog shake responses to 5-HT2 receptor stimulation in rats
K Suemaru1, H Araki, Y Kitamura
1Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Rationale:
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.
Objectives:
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.
