Acute reduction of brain substance P induced by nicotine.

Ten minutes after a single injection of 0.8 mg/kg nicotine SC (free base) the level of substance P-like immunoreactivity (SPLI) was reduced by 61-73% in rat caudate-putamen, nucleus accumbens, and olfactory tubercle, with smaller and not significant reductions in the frontal cortex, substantia nigra, and ventral tegmental area. The nicotinic receptor antagonist mecamylamine (1.0 mg/kg IP) prevented the reductions in SPLI. The rapidity and the degree of the changes in SPLI after nicotine exceed those previously reported for other agents and implicate substance P neurotransmission as a major component of nicotinic action.