title: Cycloheximide impairs acquisition but not extinction of cocaine self-administration.
abstract: The aim of the present study was to assess the role of de novo protein synthesis in the acquisition and extinction of cocaine self-administration. In a first experiment, rats were trained to respond for intravenous cocaine infusions (0.3 mg/kg) and a protein synthesis inhibitor, cycloheximide (CHX; 3 mg/kg, s.c.) was injected immediately after each self-administration session. In a second experiment, rats were allowed to acquire cocaine self-administration and CHX was injected immediately after subsequent extinction sessions. CHX impaired the acquisition, but not extinction, of cocaine self-administration. In control experiments, CHX (3 mg/kg) blocked c-Fos protein expression after foot-shock stress and impaired the acquisition of conditioned freezing but did not inhibit spontaneous locomotor activity and sucrose drinking. Our results suggest that: i) the acquisition and extinction of cocaine-reinforced behaviour have a different molecular basis; and ii) only the former process requires de novo protein synthesis.
authors.affiliation: Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Sobieskiego 9 St., 02-957 Warsaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Mierzejewski
authors.forename: Marek
authors.initials: M
authors.lastname: Siemiatkowski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Radwanska
authors.forename: Janusz
authors.initials: J
authors.lastname: Szyndler
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Bienkowski
authors.forename: Roman
authors.initials: R
authors.lastname: Stefanski
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kostowski
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003513:Cycloheximide / Q000009:adverse effects / Q000494:pharmacology*; D004327:Drinking Behavior / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D013395:Sucrose; D003513:Cycloheximide; D003042:Cocaine