Cycloheximide impairs acquisition but not extinction of cocaine self-administration.
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.
Mierzejewski
Pawel
P
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Sobieskiego 9 St., 02-957 Warsaw, Poland.
Siemiatkowski
Marek
M
Radwanska
Katarzyna
K
Szyndler
Janusz
J
Bienkowski
Przemyslaw
P
Stefanski
Roman
R
Kaczmarek
Leszek
L
Kostowski
Wojciech
W
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
D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D013395:Sucrose; D003513:Cycloheximide; D003042:Cocaine