Augmentation of cocaine hyperactivity in rats by systemic ghrelin.
The feeding-relevant pathway by which food deprivation (FD) 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 FD. The present experiment examined the impact of ghrelin or vehicle pretreatment on the locomotion and stereotypy induced by systemic cocaine hydrochloride. Male Sprague-Dawley rats were pretreated at -60 min with 0 or 5 nmol rat ghrelin (IP) and then injected (IP) at time 0 with 0, 2.5, 5.0, or 10.0 mg/kg cocaine. Locomotor activity was monitored over a 45-min post-cocaine period. Rats received the same ghrelin dose, but a different cocaine dose (in random order) on each of the four drug trials, with each drug trial separated by at least 2 days. Administration of 5 nmol ghrelin-0 mg/kg cocaine slightly increased locomotion relative to that of 0 nmol ghrelin-0 mg/kg cocaine. Cocaine increased locomotion as a function of dose in the 0 nmol ghrelin group, but the effect of cocaine was even greater when preceded by 5 nmol ghrelin. These results indicate that acute injection of ghrelin, at a feeding-relevant dose, augments the acute effects of cocaine on locomotion in rats.
Wellman
Paul J
PJ
Behavioral Neuroscience Program, Department of Psychology, Texas A&M University, College Station, TX 77843-4235, USA. PJW@PSYC.TAMU.EDU
Davis
Kristina W
KW
Nation
Jack R
JR
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D054439:Ghrelin; D008297:Male; D009068:Movement / Q000187:drug effects; D036361:Peptide Hormones / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation
D018765:Dopamine Uptake Inhibitors; D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D003042:Cocaine