Reduced sensitivity to reward in CB1 knockout mice.
BACKGROUND
Previous studies have demonstrated that the activation and blockade of the cannabinoid type 1 receptor (CB1) leads to an enhancement and decrease of the consumption of food and other orally ingested reinforcers, respectively.


OBJECTIVE
To gain further knowledge about the role of CB1 in sucrose/saccharin reinforcing efficacy and intake, we tested CB1 knockout (CB1-KO) and littermate wild-type (WT) control mice in several self-administration experimental protocols.


METHODS
Operant (fixed or progressive ratio schedule) and non-operant conditioning procedures were used. In addition, a choice analysis based on the "matching law" as well as a microstructural analysis of the intra-session pattern of self-administration was performed.


RESULTS
CB1-KO mice consume less sucrose under operant conditions or when using a two-bottle free choice procedure. Moreover, as revealed by additional behavioural analysis, CB1-KO mice exhibit a decreased sensitivity to the rewarding properties of sucrose. In agreement with this finding, the differences between WT and CB1-KO mice faded away when the palatability of sucrose was devaluated by adding quinine, but not when a non-caloric sweetener, saccharin, was available.


CONCLUSIONS
These results demonstrate a modulatory role of CB1 in the determination of the rewarding properties of sucrose and probably, as suggested by previous studies, other reinforcers.
Sanchis-Segura
Carles
C
Department of Psychopharmacology, Central Institute for Mental Health, CIMH, University of Heidelberg, 68159 Mannheim, Germany.
Cline
Brandon H
BH
Marsicano
Giovanni
G
Lutz
Beat
B
Spanagel
Rainer
R
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D012201:Reward; D013395:Sucrose / Q000008:administration & dosage
D043884:Receptor, Cannabinoid, CB1; D013395:Sucrose