Nicotine and amphetamine: differential tolerance and no cross-tolerance for ingestive effects

Rats chronically treated twice daily with nicotine (0.4 mg/kg, SC) or d,1-amphetamine (1.5 mg/kg, SC) exhibited different patterns of anorexia, hypodipsia, and body weight loss. Amphetamine-treated rats developed tolerance to these ingestive effects and to weight loss, whereas nicotine-injected rats did not. There was little, if any, evidence for cross-tolerance when the drugs were switched between the two groups. These results indicate that different mechanisms underlie the ingestive effects of nicotine and amphetamine.