We present evidence that intermittent administration of nicotine, 2 mg/kg s
.c., four times daily to mice for 14 days produces a somatic abstinence syn
drome after discontinuing treatment. The nicotine abstinence was mild and p
rotracted, lasting more than 92 h. The constellation of abstinence signs wa
s characterized by rearing, jumping, shakes, abdominal constrictions, chewi
ng, facial tremor and scratching. No autonomic symptomatology was observed.
Nicotine abstinence was attenuated with a single dose of nicotine administ
ered at 24 or 48 h into withdrawal. The nicotinic antagonist mecamylamine,
3 mg/kg, induced a small increase in the total abstinence score when given
60 min after the last nicotine injection. Nicotine-abstinent mice displayed
reduced locomotor activity. Finally, mice lost weight during the nicotine
treatment which was not recovered during the withdrawal. Along with the rat
nicotine abstinence model, the mouse model of intermittent nicotine admini
stration and abstinence might be useful for studying the pharmacological an
d biochemical mechanisms of nicotine addiction and tobacco use. (C) 1999 El
sevier Science B.V. All rights reserved.