title: Effects of cocaine self-administration and extinction on D2 -like and A2A receptor recognition and D2 -like/Gi protein coupling in rat striatum.
abstract: Striatal adenosine (A)2 -dopamine (D)2 receptor (R) heteromers exist with antagonistic interactions. We have studied these Rs and their interactions during cocaine self-administration and extinction using a 'yoked' protocol to understand the role of motivational mechanisms behind the adaptive observed. In the ventral striatum, a significant increase in the A2A R density was observed in rats that received 'yoked' cocaine during maintenance phase and following its extinction while this significant increase was only observed after extinction from cocaine self-administration. In the dorsal striatum, a significant increase in the affinity of A2A Rs was determined in the two groups of rats that received cocaine during maintenance. D2 -like Rs were significantly increased in the dorsal striatum of animals that received 'yoked' cocaine during maintenance. In the rat dorsal, but not the ventral, striatum significant reductions in the EC50 values for dopamine and increases in the guanosine5'-([γ]-thio)triphosphate (GTPγS) accumulation were observed following active and passive cocaine injections during maintenance. After 10-day extinction, a significant reduction of the Bmax value of GTPγS accumulation was demonstrated in the dorsal striatum of rats previously self-administered cocaine, while a significant reduction of the EC50 value for dopamine in the ventral striatum was found in the 'yoked' cocaine group. By comparing the cocaine self-administration group with the 'yoked' cocaine group, evidence for the existence of motivational mechanisms that guide adaptive changes in the A2A R and D2 R and in the D2 -Gi coupling differentially developed in the ventral and dorsal striatum during cocaine maintenance and its extinction has been demonstrated.
authors.affiliation: Institute of Pharmacology Polish Academy of Sciences, Department of Pharmacology, Smetna 12, Kraków, Poland. frankow@if-pan.krakow.pl
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Frankowska
authors.forename: Daniel
authors.initials: D
authors.lastname: Marcellino
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Adamczyk
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Filip
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D058908:Adenosine A2 Receptor Agonists; D018765:Dopamine Uptake Inhibitors; D044388:GTP-Binding Protein gamma Subunits; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D003042:Cocaine; D000241:Adenosine