Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats

Andrew D. Morgan, Una C. Campbell, Ryen D. Fons, Marilyn E Carroll

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84 Scopus citations


Escalation of drug intake reliably occurs when animals are allowed extended self-administration access. As a form of plasticity, escalation of drug intake may be accompanied by neuroadaptive changes that are related to the transition from controlled use to addiction. The purpose of the present experiment was to examine the effects of agmatine (decarboxylated L-arginine) on the escalation of intravenous (iv) fentanyl and cocaine self-administration in rats. Subjects were allowed 12 h of daily access to fentanyl (2.5 μg/kg) or cocaine (0.2 mg/kg) under a fixed-ratio (FR) 1 schedule of reinforcement for 30 days. Animals self-administering fentanyl were distributed into three groups: (1) low-dose agmatine (10 mg/kg) throughout self-administration; (2) high-dose agmatine (30 mg/kg) throughout self-administration; and (3) high-dose agmatine after significant escalation (Day 18) of drug intake had occurred. Animals in a fourth group were pretreated with a high dose of agmatine throughout 30 days of cocaine self-administration. Both doses of agmatine, when given throughout self-administration, significantly decreased the escalation of responding that occurred for fentanyl but not cocaine. In the group that received agmatine after significant escalation had occurred, fentanyl-maintained responding was not significantly altered. These data indicate that agmatine attenuates the escalation of fentanyl self-administration if administered before the escalation begins and may mediate neuroadaptive events related to chronic opioid self-administration.

Original languageEnglish (US)
Pages (from-to)873-880
Number of pages8
JournalPharmacology Biochemistry and Behavior
Issue number4
StatePublished - 2002

Bibliographical note

Funding Information:
The authors are grateful to Kelly P. Cosgrove and Megan E. Roth for critically reviewing this manuscript, as well as to Drs. Carolyn Fairbanks and George Wilcox for their discussions of dosing and experimental design, and Bao Do, Beth Drewitz, Paul Drewitz, Christina Gremel and Jennifer Mickelberg for their technical assistance. This study was supported by NIDA grants R37 DA03240 (M.E.C.), T32 DA07097 (U.C.C.) and NCCAM grant T32 AT00009-02 (A.D.M.).


  • Agmatine
  • Cocaine
  • Escalation
  • Fentanyl
  • Intravenous
  • NMDA antagonist
  • NOS inhibitor
  • Self-administration
  • Sensitization
  • Tolerance


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