Nicotine attenuates DOI-induced head-twitch response in mice: implications for Tourette syndrome.
Tourette syndrome (TS), a chronic neuropsychiatric disorder, is characterized by motor and vocal tics. Preliminary clinical studies indicate possible therapeutic benefits of nicotine in the treatment of Tourette's syndrome (TS). It has been proposed that twitches of the head in mice or twitches of head and shoulders in rats following administration of the selective 5HT(2A/C) agonist DOI (1-)2,5-dimethoxy-4-iodophenyl-2-aminopropane, can serve as an animal model of tics in TS. In this study, the effects of acute and chronic administration of nicotine on DOI-induced head twitch response (HTR) in male albino ICR mice were evaluated. Both acute and chronic nicotine (daily injections for 10 days) reduced the DOI-induced HTR. Moreover, chronic administration of DOI (1 mg/kg/day for 10 days) resulted in 65% increase in [125I]alpha-bungarotoxin binding in cerebellum and 41% increase in striatal [3H]cytisine binding. However, the acute inhibitory effects of nicotine were not blocked by pretreatment with the nicotinic antagonist, mecamylamine. Indeed, at higher doses, mecamylamine also reduced the DOI-induced HTR. The data suggest that both nicotine and mecamylamine may be of therapeutic potential in the treatment of some symptoms of TS.
Tizabi
Y
Y
Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, USA. ytizabi@howard.edu
Russell
L T
LT
Johnson
M
M
Darmani
N A
NA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D019416:Head Movements / Q000187:drug effects* / Q000502:physiology; D007215:Indophenol / Q000009:adverse effects* / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000009:adverse effects*; D020323:Tics / Q000139:chemically induced / Q000188:drug therapy; D005879:Tourette Syndrome / Q000378:metabolism / Q000517:prevention & control*
D018722:Nicotinic Agonists; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; D007215:Indophenol; D009538:Nicotine