Sensitization to caffeine and cross-sensitization to amphetamine: influence of individual response to caffeine

The present study evaluated the ability of a subchronic intermittent administration of caffeine to induce a sensitized motor response and correlated the individual susceptibility of rats to acute caffeine to the development of sensitization. Moreover, individual susceptibility to caffeine and development of motor behaviour sensitization were correlated to the behavioural response obtained after a challenge with amphetamine. To this end, rats were subdivided in "low" and "high" responders according to their individual susceptibility to acute caffeine established on the basis of the motor activity observed after the first caffeine administration. "Low" and "high" responder rats were then repeatedly and intermittently treated with caffeine (15 mg/kg, i.p.), or vehicle, every other day for fourteen days. Three days after treatment discontinuation, behavioural activation induced by acute amphetamine (0.5 mg/kg, s.c.) was measured in vehicle- and caffeine-pretreated rats. Subchronic caffeine resulted in motor sensitization of a variable degree among rats and no difference were observed between "low" and "high" responders. Moreover, caffeine pretreatment potentiated the behavioural effects of amphetamine according to the degree of caffeine sensitization but not to individual susceptibility to acute caffeine. These results demonstrate that individual susceptibility to acute caffeine does not influence the modifications in caffeine motor effects produced by its subchronic administration and does not affect the enhancement of acute behavioural effects of amphetamine in caffeine-pretreated rats, rather sensitization to subchronic caffeine administration critically influences the behavioural effects of amphetamine.