A decrease in gamma-synuclein expression within the nucleus accumbens increases cocaine intravenous self-administration in the rat.
Except as a marker of cancer progression, gamma-synuclein (GSyn) had received little attention. Recent data showed however that GSyn modulates cocaine-induced locomotor effects, suggesting that it could also play a role in cocaine reinforcing effects. In the rat, siRNAs targeting GSyn expression were injected in the nucleus accumbens and cocaine reinforcing effects were evaluated by means of intravenous self-administration. A dose-response curve was followed by procedures of progressive ratio, extinction, cocaine- and cue-induced reinstatements. Decrease of GSyn expression increased self-administration over a large range of doses. This effect was associated with an increase in cocaine-induced reinstatement. The present data reveal that GSyn exert a specific negative control on cocaine-induced reinforcing and incentive effects.
Boyer
Frédéric
F
Institute of Biochemistry, University of Fribourg, Switzerland.
Balado
Eric
E
Piazza
Pier V
PV
Dreyer
Jean-Luc
JL
Deroche-Gamonet
Véronique
V
D000818:Animals; D001245:Association Learning / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000503:physiopathology; D003216:Conditioning, Operant / Q000502:physiology; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000502:physiology; D015870:Gene Expression / Q000235:genetics*; D009042:Motivation / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000473:pathology / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012055:Reinforcement Schedule; D012646:Self Administration; D015819:Substance Abuse, Intravenous / Q000235:genetics* / Q000473:pathology; D051845:gamma-Synuclein / Q000235:genetics*
D034741:RNA, Small Interfering; D051845:gamma-Synuclein; D003042:Cocaine