The development of tolerance to amphetamine-induced hypophagia was assessed by recording changes in lick parameters in rats given chronic administration of the drug (2 mg/kg) and access to sweetened milk. Although licking and milk intake gradually recovered, the volume of milk ingested per lick remained suppressed. Amphetamine had no effect on the interlick interval or the force per lick. In contrast, the drug caused a sustained increase in the number of lick bursts (defined by pause criteria of 0.5-2.0 s) and a decrease in the number of licks per burst (but only at pause criteria of 0.5 and 1.0 s). These results suggest that tolerant rats frequently interrupt licking, resulting in less efficient capture of milk.

To analyze how tolerance develops to amphetamine-induced hypophagia, the authors recorded real-time licking responses in rats given chronic injections of the drug and access to milk for 30 min. Initially, licking was greatly reduced and occurred only late in the session. The acquisition of tolerance was characterized by a decrease in the latency to initiate licking, a gradual increase in the number of licks, and a reorganization of the temporal licking pattern such that licks were distributed throughout the session, interspersed with pauses. On post-tolerance dose-response tests, licking was directly proportional to drug dose in some rats. The results support the view that tolerance to amphetamine hypophagia involves a behavioral adaptation to the motor effects of the drug.

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