The feeding-relevant pathway by which food restriction (FR) augments cocaine action is unknown. Systemic administration of the 28-amino acid acylated peptide ghrelin (1-10 nmol) increases food intake in rats and circulating levels of rat ghrelin are up-regulated by FR. The present experiment examined the impact of repeated administration of ghrelin or vehicle on the subsequent capacity of cocaine to enhance locomotion in rats. Male Sprague-Dawley rats were pretreated daily for seven days with 0, 5 or 10 nmol rat ghrelin (i.p.) in the home cage. On the 8th day, rats were transported to a testing room, placed in a locomotion chamber for 15 min, and then injected (i.p.) with 0, 7.5, or 15 mg/kg cocaine hydrochloride. Locomotor activity was monitored over a 45 min post-cocaine period. Pretreatment with 5 or 10 nmol ghrelin alone did not significantly increase basal locomotion relative to that of the 0 nmol ghrelin group. Rats pretreated with 5 nmol or 10 nmol ghrelin showed an enhanced locomotor response after treatment with 15 mg/kg cocaine relative to rats treated with 0 nmol ghrelin. These results indicate that acute injection of ghrelin, at a feeding-relevant dose, can augment the acute effects of cocaine on locomotion in rats.