Lucyna Pomierny-Chamiolo1, Joanna Miszkiel2, Malgorzata Frankowska2, Józef Mizera3, Malgorzata Filip2. 1. Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: lpomiern@cm-uj.krakow.pl. 2. Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Kraków, Poland. 3. Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland.
Abstract
BACKGROUND: In the cocaine addiction the development from transient into persistent neuroplastic changes strongly involves the glutamatergic system. In this respect, among glutamatergic receptors special attention is paid to the group II of metabotropic glutamatergic receptors (mGlu2/3R) which are involved in the transition from drug use to drug addiction including the relapse mechanisms. METHODS: The present study employed radioligand binding and Western blot assays to study mGlu2/3R density, affinity and protein expression in selected rat brain areas after cocaine self-administration, extinction training and cocaine-induced reinstatement. Rats were randomly assigned in triads to one of three conditions: contingent cocaine intravenous self-administration, non-contingent injections of cocaine (yoked cocaine), or saline yoked to the intake of the self-administering subject. RESULTS: Cocaine self-administration and yoked cocaine delivery resulted in a significant increase in the mGlu2/3R density in the prefrontal cortex and the dorsal striatum, while 10-day extinction training provoked a reduction in the prefrontal cortex and the nucleus accumbens. Cocaine abstinence also enhanced an increase in the [3H]ligand binding to mGlu2/3R in the prefrontal cortex. During reinstatement the cocaine challenge dose (10mg/kg, ip) led to important elevation in the mGlu2/3R density in the prefrontal cortex. CONCLUSIONS: Our study demonstrated the role of mGlu2/3R localized in the prefrontal cortex-striatum pathways to cocaine repeated exposure.
BACKGROUND: In the cocaine addiction the development from transient into persistent neuroplastic changes strongly involves the glutamatergic system. In this respect, among glutamatergic receptors special attention is paid to the group II of metabotropic glutamatergic receptors (mGlu2/3R) which are involved in the transition from drug use to drug addiction including the relapse mechanisms. METHODS: The present study employed radioligand binding and Western blot assays to study mGlu2/3R density, affinity and protein expression in selected rat brain areas after cocaine self-administration, extinction training and cocaine-induced reinstatement. Rats were randomly assigned in triads to one of three conditions: contingent cocaine intravenous self-administration, non-contingent injections of cocaine (yoked cocaine), or saline yoked to the intake of the self-administering subject. RESULTS:Cocaine self-administration and yoked cocaine delivery resulted in a significant increase in the mGlu2/3R density in the prefrontal cortex and the dorsal striatum, while 10-day extinction training provoked a reduction in the prefrontal cortex and the nucleus accumbens. Cocaine abstinence also enhanced an increase in the [3H]ligand binding to mGlu2/3R in the prefrontal cortex. During reinstatement the cocaine challenge dose (10mg/kg, ip) led to important elevation in the mGlu2/3R density in the prefrontal cortex. CONCLUSIONS: Our study demonstrated the role of mGlu2/3R localized in the prefrontal cortex-striatum pathways to cocaine repeated exposure.
Authors: Nuria García-Marchena; Alberto Marcos; María Flores-López; Mario Moreno-Fernández; Nerea Requena-Ocaña; Oscar Porras-Perales; Sandra Torres-Galván; Pedro Araos; Antonia Serrano; Roberto Muga; Juan Jesús Ruiz-Ruiz; Fernando Rodríguez de Fonseca; Emilio Ambrosio; Francisco Javier Pavón-Morón Journal: Biomedicines Date: 2022-05-14
Authors: L Blazquez-Llorca; M Miguéns; M Montero-Crespo; A Selvas; J Gonzalez-Soriano; E Ambrosio; J DeFelipe Journal: Cereb Cortex Date: 2021-03-05 Impact factor: 5.357