Intraperitoneal (i.p.) administration of nicotine to rats induced purp
oseless chewing. The response induced by different doses of the drug (
0.0001, 0.001, 0.01 and 0.1 mg/kg) seems to be dose dependent, with a
maximum effect at 0.01 mg/kg and then decreasing at a higher dose (0.1
mg/kg). Pre-treatment of animals with the nicotine antagonist mecamyl
amine (0.01 and 0.1 mg/kg, 30 min) and the D-2 receptor antagonist sul
piride (12.5-100 mg/kg, 90 min), but not the D-1 antagonist SCH 23390
(0.01 and 0.05 mg/kg, 30 min), decreased the chewing induced by nicoti
ne (0.01 mg/kg). When animals were pre-treated with propranolol (5 and
10 mg/kg) 60 min, reserpine (2.5 mg/kg) 18 h or alpha-methyl-p-tyrosi
ne (alpha-MPT; 250 mg/kg) 60 min before nicotine, the effect of the dr
ug was reduced. However, reserpine (2.5 mg/kg) at 18 h plus alpha-MPT
(250 mg/kg) 60 min prior to nicotine completely inhibited the drug res
ponse. Pre-treatment of animals with phenoxybenzamine (2.5 and 5 mg/kg
i.p., 60 min) or atropine (5 and 10 mg/kg) did not change the nicotin
e response significantly. It is concluded that nicotine-induced purpos
eless chewing is mediated through dopaminergic and nicotinic mechanism
s.