Research paperEffects of ketamine and n-methyl-d-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268
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Animals and surgery
Male Sprague–Dawley rats (300–350 g) were purchased from Harlan (San Diego, CA, USA) and were maintained under a 12-h light/dark cycle. All microdialysis experiments occurred during the light phase of the light/dark cycle. All procedures were performed in accordance with The Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee. The total number of animals as well as their suffering was minimized whenever possible. Before and after
Effects of ketamine on glutamate and DA release
For glutamate-release studies, 24 control animals received an 18 mg/kg s.c. ketamine challenge injection (Fig. 1). These 24 animals are a compilation of three separate groups, each serving as a control group for one of three treatment groups; 1) systemic LY379268 (3 mg/kg), 2) local LY379268 (1 μM) and 3) TTX (1 μM). Here we report on the pooled data (24 subjects). In the section to follow individual control groups are analyzed with respect to their treatment group. The ANOVA conducted on the
Discussion
We demonstrate that the mGluR2/3-selective agonist LY379268 blocks ketamine-evoked as well as NMDA-evoked glutamate release in the mPFC of the awake rat. Systemic administration of ketamine and local infusion of NMDA increased glutamate release; pretreating animals with a systemic injection of LY379268 blocked both effects. Locally applied LY379268 into the mPFC also prevented the increase in glutamate release evoked by ketamine (but not by NMDA). These results suggest that stimulation of
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