Impairment of endocannabinoids activity in the dorsolateral striatum delays extinction of behavior in a procedural memory task in rats.
The dorsolateral striatum (DLS) has been implicated in the learning of habits and procedural memories. Extinction of this kind of memories has been poorly studied. The DLS expresses high levels of the cannabinergic receptor one (CB1), and, lately, it has been suggested that the activation of CB1 in this structure is indispensable for long-term depression (LTD) development. We performed experiments in a T-maze and evaluated the effects of intrastriatal and intrahipocampal administration of the CB1 antagonist AM251 on extinction and on c-Fos expression. We also administered anandamide to evaluate if an artificial increase of endocannabinoids facilitates extinction. Our results indicate clearly a dose-response blockade of extinction induced by AM251 injected into the striatum but a facilitation of extinction when administered into the hippocampus. Anandamide did not induce any observable changes. AM251 effects were accompanied by an increase in c-Fos immunoreactivity in the DLS and its decrease in the hippocampal region, suggesting that the activation of CB1 in the striatum is necessary for the extinction of procedural memories. These findings could be important in some neurological conditions, such as obsessive-compulsive disorder in which striatal activity seems to be abnormal.
Rueda-Orozco
Pavel E
PE
Grupo de Neurociencias, Departmento de Fisiología, Facultad de Medicina, UNAM, Laboratorio 601, Apartado Postal 70-250, Mexico City, D.F. 04510, Mexico. pavel.rueda@gmail.com
Montes-Rodriguez
Corinne J
CJ
Soria-Gomez
Edgar
E
Méndez-Díaz
Mónica
M
Prospéro-García
Oscar
O
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004334:Drug Administration Schedule; D063388:Endocannabinoids; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013223:Statistics as Topic
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; C103505:AM 251; C078814:anandamide