title: Involvement of AMPA/Kainate Glutamate Receptor in the Extinction and Reinstatement of Morphine-Induced Conditioned Place Preference: A Behavioral and Molecular Study.
abstract: Glutamate receptors in mesolimbic areas such as the nucleus accumbens, ventral tegmental area, prefrontal cortex (PFC), and hippocampus (HIP) are a component of the mechanisms of drug-induced reward and can modulate the firing pattern of dopaminergic neurons in the reward system. In addition, several lines of study have indicated that cAMP response element-binding protein (CREB) and c-fos have important role in morphine-induced conditioned place preference (CPP) induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated CREB (p-CREB) and c-fos induction within the nucleus accumbens (NAc), HIP, and PFC after intracerebroventricular (ICV) administration of different doses of CNQX or vehicle during extinction period or reinstatement of morphine-induced CPP. In all groups, the CPP procedure was done; afterward, the conditioning scores were recorded by Ethovision software. After behavioral test recording, we dissected out the NAc, HIP, and PFC regions and measured the p-CREB/CREB ratio and c-fos level by Western blot analysis. Our results showed that administration of CNQX significantly shortened the extinction of morphine CPP. Besides, ICV microinjection of CNQX following extinction period decreased the reinstatement of morphine CPP in extinguished rats. In molecular section, in treatment group, all mentioned factors were dose-dependently decreased in comparison with vehicle group (DMSO) after ICV microinjection of different doses of CNQX but not in pre-extinction microinjection. These findings suggested that antagonism of AMPA receptor decreased p-CREB/CREB ratio and c-fos level in the PFC, NAc, and HIP. Modulation of the drug memory reconsolidation may be useful for faster extinction of drug-induced reward and attenuation of drug-seeking behavior.
authors.affiliation: Department of Physiology and Pharmacology, Mazandaran University of Medical Sciences, Ramsar International Branch, Sari, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Siahposht-Khachaki
authors.affiliation: Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fatahi
authors.affiliation: Neurobiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Asal
authors.initials: A
authors.lastname: Yans
authors.affiliation: Neurobiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran. haghparast@yahoo.com.
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D057967:Infusions, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018691:Excitatory Amino Acid Antagonists; D009020:Morphine; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors
keywords: AMPA/kainate receptor; Extinction; Reinstatement; Reward; c-fos induction; p-CREB/CREB ratio