An acute dose of racemic gamma vinyl-GABA (GVG) attenuates the acute effects of morphine on brain metabolism and behavior in young adult animals

417 Objectives We examined the ability of racemic GVG to inhibit morphine-induced changes in brain metabolism and behavior in young adult animals (PND 50). Small animal PET imaging using 18FDG was coupled with behavioral measures during uptake following an acute dose of morphine (10 mg/kg, Group 1) or an acute dose of morphine (10 mg/kg) and GVG (100 mg/kg, Group 2). Methods Two groups of freely moving young adult male Sprague-Dawley rats (n=7/group) were studied using an Siemen9s Inveon. All animals received baseline 18FDG scans. Group 1 animals received an acute challenge of morphine (10 mg/kg) and were rescanned following their challenge. Group 2 animals received the identical morphine dose and scanning regimen as Group 1 except with the addition of GVG (100 mg/kg) prior to morphine. An observational time-sampling procedure was used to record behaviors during 18FDG uptake. Composite behavioral scores established individual drug severity as well as group differences. Results Marked changes in 18FDG uptake were noted in both cortical and subcortical structures in Group 1 animals (morphine only challenge). In contrast, however, these metabolic changes were either blocked or significantly reduced following the addition of GVG. Similar changes were noted in behaviors associated with an acute morphine challenge. Conclusions GVG blocks or inhibits morphine-induced changes in brain metabolism in young adult animals. These data support the continued development of GVG for the potential treatment of opiate dependence and withdrawal. Perhaps more importantly, these data further validate the use of small animal PET with 18FDG in behaving animals in an effort to better understand neural circuits that underlie behavior. This combined strategy of awake animal imaging may ultimately provide a novel platform to better guide CNS drug development. Research Support Supported by the NIH and the DoD (K02-DA22346 to SLD; RC1-E4018534, PR094020 and DA25729 to WKS)