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 nmol/side) or saline was microinjected into the region five minutes prior to a challenge cocaine injection. Our data showed that intra-mPFC mGluR5 blockade via MTEP prevented late, but not early, behavioral sensitization. Further, intra-mPFC mGluR5 activation via DHPG (30 uM) increased mPFC and NAc glutamate levels in sensitized animals during early and late withdrawal, respectively. Finally, we observed a nonsignificant trend toward an MTEP-induced reduction in drug-seeking following the presentation of a cocaine-associated cue in animals that had been trained to selfadminister cocaine. Taken together, our data suggest mPFC mGluR5 plays a role in cocaine addiction, possibly through the modulation of mPFC pyramidal neuronal excitability
","abstract_html":"<p>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 nmol/side) or saline was microinjected into the region five minutes prior to a challenge cocaine injection. Our data showed that intra-mPFC mGluR5 blockade via MTEP prevented late, but not early, behavioral sensitization. Further, intra-mPFC mGluR5 activation via DHPG (30 uM) increased mPFC and NAc glutamate levels in sensitized animals during early and late withdrawal, respectively. Finally, we observed a nonsignificant trend toward an MTEP-induced reduction in drug-seeking following the presentation of a cocaine-associated cue in animals that had been trained to selfadminister cocaine. Taken together, our data suggest mPFC mGluR5 plays a role in cocaine addiction, possibly through the modulation of mPFC pyramidal neuronal excitability</p>","abstract_has_math":false,"creators":["Timmer, Kristin Marie"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Jeffrey Steketee, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-12-01T08:00:00Z","date_published":"2012-12-01T08:00:00Z","updated_at":"2026-07-24T05:00:17Z","subjects":["cocaine","medial prefrontal cortex","metabotropic glutamate receptor 5","Medical Molecular Biology","Medical Neurobiology","Medical Sciences","Medicine and Health Sciences","Mental and Social Health","Neurosciences","Substance Abuse and Addiction"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/272","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Jeffrey Steketee, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Timmer, Kristin Marie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-06-17T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cocaine","medial prefrontal cortex","metabotropic glutamate receptor 5","Medical Molecular Biology","Medical Neurobiology","Medical Sciences","Medicine and Health Sciences","Mental and Social Health","Neurosciences","Substance Abuse and Addiction"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/272"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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 nmol/side) or saline was microinjected into the region five minutes prior to a challenge cocaine injection. Our data showed that intra-mPFC mGluR5 blockade via MTEP prevented late, but not early, behavioral sensitization. Further, intra-mPFC mGluR5 activation via DHPG (30 uM) increased mPFC and NAc glutamate levels in sensitized animals during early and late withdrawal, respectively. Finally, we observed a nonsignificant trend toward an MTEP-induced reduction in drug-seeking following the presentation of a cocaine-associated cue in animals that had been trained to selfadminister cocaine. Taken together, our data suggest mPFC mGluR5 plays a role in cocaine addiction, possibly through the modulation of mPFC pyramidal neuronal excitability
"]},{"key":"dc:title","label":"Title","values":["Metabotropic Glutamate Receptor 5 in the Medial Prefrontal Cortex: Role in Cocaine Sensitization and Addiction"]}]}],"canonical_facts":{"dc:contributor":["Jeffrey Steketee, Ph.D."],"dc:creator":["Timmer, Kristin Marie"],"dc:date.available":["2016-06-17T07:00:00Z"],"dc:description.abstract":["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 nmol/side) or saline was microinjected into the region five minutes prior to a challenge cocaine injection. Our data showed that intra-mPFC mGluR5 blockade via MTEP prevented late, but not early, behavioral sensitization. Further, intra-mPFC mGluR5 activation via DHPG (30 uM) increased mPFC and NAc glutamate levels in sensitized animals during early and late withdrawal, respectively. Finally, we observed a nonsignificant trend toward an MTEP-induced reduction in drug-seeking following the presentation of a cocaine-associated cue in animals that had been trained to selfadminister cocaine. Taken together, our data suggest mPFC mGluR5 plays a role in cocaine addiction, possibly through the modulation of mPFC pyramidal neuronal excitability
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/272"],"dc:subject":["cocaine","medial prefrontal cortex","metabotropic glutamate receptor 5","Medical Molecular Biology","Medical Neurobiology","Medical Sciences","Medicine and Health Sciences","Mental and Social Health","Neurosciences","Substance Abuse and Addiction"],"dc:title":["Metabotropic Glutamate Receptor 5 in the Medial Prefrontal Cortex: Role in Cocaine Sensitization and Addiction"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:17Z"}