Caffeine elevates reinforcement threshold for electrical brain stimulation: tolerance and withdrawal changes

Caffeine dose-dependently increased the reinforcement threshold for electrical self-stimulation of the brain in rats, which is opposite to the effect of other behavioral stimulants. Tolerance to this effect of caffeine developed rapidly with daily drug administration. Abrupt cessation of daily drug treatment was followed by decreases in reinforcement threshold and response rate lasting 24-48 h, changes consistent with a drug withdrawal phenomenon. Because caffeine has the characteristics of a drug of abuse, these results question the generality of hypotheses relating the abuse potential of a drug to its ability to sensitize brain reward systems.