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Metabotropic Glutamate Receptor 5 In The Medial Prefrontal Cortex: Role In Cocaine Sensitization And Addiction, Kristin Marie Timmer
Metabotropic Glutamate Receptor 5 In The Medial Prefrontal Cortex: Role In Cocaine Sensitization And Addiction, Kristin Marie Timmer
Theses and Dissertations (ETD)
Cocaine sensitization is associated with cocaine-induced hyperexcitability of pyramidal projection neurons within the medial prefrontal cortex (mPFC). Such hyperexcitability presumably results in increased glutamatergic input to reward-affiliated brain regions such as the ventral tegemental area (VTA) and nucleus accumbens (NAc), consequently facilitating drugseeking behavior. Metabotropic glutamate receptor 5 (mGluR5) has been implicated in cocaine addiction and demonstrated to increase neuronal excitability, therefore, the aim of the present study was to investigate the effect of intra-mPFC mGluR5 manipulation on behavioral and neurochemical sensitization and drug-seeking. Bilateral cannulae were implanted into the mPFC of male Sprague-Dawley rats and mGluR5 antagonist MTEP (15 …
Role Of Medial Prefrontal Cortical Group Ii Metabotropic Glutamate Receptor In The Development Of Cocaine Sensitization, Xiaohu Xie
Theses and Dissertations (ETD)
The current studies examined the role of medial prefrontal cortical (mPFC) group II metabotropic glutamate receptors (mGluR2/3) in the development of cocaine sensitization. Initial studies demonstrated that intra-mPFC injection of the mGluR2/3 receptor agonist, APDC, dose-dependently reduced acute behavioral response to cocaine (0.015-15 nmol/side with significant effects starting at 1.5nmol/side). The effects of APDC were prevented by intra-mPFC co-injections of an mGluR2/3 antagonist, LY341495 (1.5 nmol/side). Repeated intra-mPFC APDC (1.5 nmol/side) injections also prevented the initiation of behavioral and neurochemical sensitization, which is defined as enhanced nucleus accumbens (NAc) dopamine response to cocaine. Once sensitization was …