Cessation of chronic nicotine administration enhances wet-dog shake responses to 5-HT₂ receptor stimulation in rats

Rationale: The involvement of central serotonergic systems has been hypothesized clinically to contribute to nicotine withdrawal symptoms. However, involvement of the serotonin2 (5-HT₂) receptor system in nicotine withdrawal is not clear. Objectives: The changes in wet-dog shake responses induced by (±)-1-(2,5-di-methoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT₂ 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-HT₂ receptor systems, and that the 5-HT₂ receptor systems may be involved in the nicotine withdrawal symptoms.