Agmatine reduces opioid-induced tolerance and self-administration. Conversely, anti-agmatine IgG sensitizes rodents to these phenomena (Morgan-AD, SfN 2004). We evaluated the presence of endogenous agmatine in regions that drive these events. HPLC analysis was conducted on mouse CNS tissue and serum extracted following intrathecal and intracerebroventricular administration of agmatine. The concentration-time profile and the duration of agmatine pharmacodynamics were determined. Additionally, the localization of agmatine in spinal cord and in nucleus accumbens was conducted using selective anti-agmatine IgG. Effects of agmatine immunoneutralization were also evaluated. After intrathecal delivery peak agmatine concentrations were detected in spinal cord within 6 hours. An apparent elimination phase was evident up to 3 days. Intrathecal agmatine inhibition of NMDA-evoked pharmacodynamic measures was maximal at co-injection and ineffective at five minutes. Following ICV administration peak agmatine concentrati...