title: Agmatine attenuates the discriminative stimulus and hyperthermic effects of methamphetamine in male rats.
abstract: Methamphetamine abuse remains an alarming public heath challenge, with no approved pharmacotherapies available. Agmatine is a naturally occurring cationic polyamine that has previously been shown to attenuate the rewarding and psychomotor-sensitizing effects of methamphetamine. This study examined the effects of agmatine on the discriminative stimulus and hyperthermic effects of methamphetamine. Adult male rats were trained to discriminate 0.32 mg/kg methamphetamine from saline. Methamphetamine dose dependently increased drug-associated lever responding. The nonselective dopamine receptor antagonist haloperidol (0.1 mg/kg) significantly attenuated the discriminative stimulus effects of methamphetamine (5.9-fold rightward shift). Agmatine (10-100 mg/kg) did not substitute for methamphetamine, but significantly attenuated the stimulus effects of methamphetamine, leading to a maximum of a 3.5-fold rightward shift. Acute 10 mg/kg methamphetamine increased the rectal temperature by a maximum of 1.96±0.17°C. Agmatine (10-32 mg/kg) pretreatment significantly attenuated the hyperthermic effect of methamphetamine. Agmatine (10 mg/kg) also significantly reversed methamphetamine-induced temperature increase. Together, these results support further exploration of the value that agmatine may have for the treatment of methamphetamine abuse and overdose.
authors.affiliation: aDepartment of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA bDepartment of Neurosurgery, Binzhou People's Hospital, Binzhou, Shandong Province, China.
authors.forename: David A
authors.initials: DA
authors.lastname: Thorn
authors.forename: Jiuzhou
authors.initials: J
authors.lastname: Li
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Qiu
authors.forename: Jun-Xu
authors.initials: JX
authors.lastname: Li
mesh_terms: D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
chemical_list: D018492:Dopamine Antagonists; D008694:Methamphetamine; D000376:Agmatine; D006220:Haloperidol