Effects of serotonin (5-HT)2 receptor ligands on depression-like behavior during nicotine withdrawal.
A pronounced withdrawal syndrome including depressed mood prevents cigarette smoking cessation. We tested if blockade or activation of serotonin (5-HT)(2) receptors affected the time of immobility (as an indirect measure of depression-like behavior) in naïve animals and in those withdrawn from chronic nicotine in the forced swim test (FST). The antidepressant imipramine was used as a control. In the FST, the selective 5-HT(2A) receptor antagonist M100,907 (1-2 mg/kg, but not 0.5 mg/kg), the selective 5-HT(2C) receptor antagonist SB 242,084 (0.3-1 mg/kg, but not 0.1 mg/kg), the 5-HT(2C) receptor agonists Ro 60-0175 (10 mg/kg, but not 3 mg/kg) and WAY 163,909 (1.5-10 mg/kg, but not 0.75 mg/kg) as well as imipramine (30 mg/kg, but not 15 mg/kg) decreased the immobility time while the non-selective 5-HT(2) receptor agonist DOI (0.1-1 mg/kg) was inactive in naïve rats. We found an increase in immobility time in rats that were withdrawn from nicotine exposure after 5 days of chronic nicotine treatment. This effect increased from day 1 until day 10 following withdrawal of nicotine, with maximal withdrawal effects on day 3. M100,907 (1 mg/kg), SB 242,084 (0.3 mg/kg), Ro 60-0175 (3 mg/kg), WAY 163,909 (0.75-1.5 mg/kg) and imipramine (15-30 mg/kg) shortened the immobility time in rats that had been removed from nicotine exposure for 3 days. Locomotor activity studies indicated that the effects of SB 242,084 might have been non-specific, as we noticed enhanced basal locomotion in naïve rats. This data set demonstrates that 5-HT(2A) receptor antagonist and 5-HT(2C) receptor agonists exhibited effects similar to antidepressant drugs and abolished the depression-like effects in nicotine-withdrawn rats. These drugs should be considered as adjuncts to smoking cessation therapy, to ameliorate abstinence-induced depressive symptoms.
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland. zaniew@if-pan.krakow.pl
Magdalena
M
Zaniewska
Andrew C
AC
McCreary
Karolina
K
Wydra
Małgorzata
M
Filip
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D013550:Swimming; D013997:Time Factors; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D018722:Nicotinic Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D009538:Nicotine; D007099:Imipramine