Table 1 Preclinical data in genetically modified mice and effect of genetic deletion of different GPCRs on alcohol intake behaviors

From: GPCR and Alcohol-Related Behaviors in Genetically Modified Mice

GPCR systemGeneAlcohol intakeDrinking paradigmReferences
OpioidOprm1−/−↓Continuous[40]
Oprm1−/−↓Continuous[41]
Oprm1−/−↓Self-administration[41]
Oprm1, 118GG carrier↑Continuous[42, 132]
Oprd1−/−↑Limited[43]
Oprd1−/−↑Self-administration[44]
Oprd1−/−↑Continuous[44]
Oprk1−/−↓Limited[43]
Oprk1−/−↓Continuous[45]
Pomc−/−↑Continuous[46]
Pomc−/−↓Continuous[47]
Penk−/−↓Continuous[47]
Penk−/−≈Continuous[48]
Pdyn−/−↑Continuous[49]
Pdyn−/−↑Continuous[50]
Oprl1−/−↓ (only at high concentrations)Continuous[51]
Oprl1−/− (in rats)↓Self-administration[52]
EndocannabinoidCnr1−/−↓Limited[53]
Cnr1−/−↓Limited[54]
Cnr1−/−↓Continuous[55]
Cnr1−/−↓Continuous[56]
Cnr1−/−↓Continuous[23]
Cnr1−/−≈Continuous[57]
Cnr2−/−↑Continuous[58]
Cnr2−/−↑Self-administration[58]
GhrelinGhsr−/−≈Limited[59]
Ghsr−/−↓Continuous[23]
Ghsr−/− (in rats)↓Self-administration[60]
Ghsr−/− (in rats)↓DID[60]
Ghsr−/− (in rats)≈Intermittent access[60]
Ghrl−/−≈Limited[61]
Ghrl−/−↓Continuous[62]
Ghrl−/−↓Continuous[23]
Mboat4−/−↓Continuous[23]
DopaminergicDrd1−/−↓Limited[63]
Drd1−/−↓Continuous[63]
Drd2−/−↓Continuous[64]
Drd2−/−↓Continuous[65]
Drd2−/−↓Continuous[66]
Drd2−/−↓Continuous[67]
Drd2−/−↓Self-administration[68]
Drd3−/−↓Limited[69]
Drd3−/−↓Continuous[69]
Drd3−/−≈Continuous[70]
Drd3−/−≈Self-administration[70]
Drd3−/−≈Limited[71]
Drd3−/−≈Continuous[71]
Drd4−/−↑Limited[72]
Serotoninergic5htr1b−/−↑Continuous[35]
5htr1b−/−↑/≈Self-administration[73]
5htr1b−/−≈Continuous[74]
5htr1b−/−≈Continuous[35]
5htr6−/−≈Continuous[75]
GlutamatergicGrm5−/−↓Continuous[76]
Grm5−/−≈Continuous[77]
Grm5−/−↓ (females only)4 bottles[77]
Grm5−/−↓ (females only)DID[77]
Grm5−/−No change (females only)Limited[77]
Grm5AA/AA↑Continuous[78]
Grm5AA/AA↑DID[78]
Grm5AA/AA↑Self-administration[78]
Grm2−/−↑ (only at high concentrations)Continuous[79]
Grm4−/−≈Continuous[80]
B6.129/Ola−Grm7tmNovartis↑Continuous[81]
CRFCrhr1−/−≈Continuous[82]
Crhr1−/−↑Stress + continuous[82]
CRF1NestinCre≈Continuous[83]
Crhr1−/−≈Continuous[83]
CRF1NestinCre↓Stress + continuous[83]
Crhr1−/−↑Stress + continuous[83]
Crhr1−/−↑Vapor exposure + continuous[83]
Crhr1−/−↓DID[84]
Crhr1−/−↓DID[85]
Crhr1−/−↓20% continuous[86]
Crhr1−/−≈3%, 6%, or 10% continuous[86]
Crhr1−/−↓Stress + continuous[86]
Crhr1−/−≈Self-administration[87]
Crhr2−/−↓DID[85]
MelanocortinMc3r−/−≈DID[88]
Mc4r−/−≈Continuous[89]
Orphan GPCRGpr88−/−↑Continuous[90]
Gpr88−/−↑Intermittent access[90]
MuscarinicChrm4−/−↑Self-administration[91]
HistamineHrh3−/−↓Continuous[92]
Hrh3−/−↓Limited DID[92]
Melanin-concentrated hormoneMchr1−/−↑Continuous[93]
Mchr1−/−≈Limited[93]
AngiotensinAgtr1a−/−↓Continuous[94]
Agtr2−/−≈Continuous[94]
BradykininBdkrb2−/−≈Continuous[94]
VasopressinAvpr1a−/−↑Continuous[95]
AdenosineAdora1−/−≈Self-administration[96]
Adora2a−/−↑Continuous[97]
Adora2a−/−≈Continuous[98]
Neuropeptide YNpy1r−/−↑Continuous[99]
Npy2r−/−↓/≈Continuous[100]
Npy5r−/−≈Continuous[101]
ChemokineCcr2−/−↓Continuous[102]
Ccr5−/−≈Continuous[102]
CholecystokininCckar−/−↑ (preference unchanged)Continuous[103]
Cckbr−/−↓/≈Continuous[103]
Cckbr−/−↑Continuous[104]
NeurokininTacr1−/−↓Continuous[105]
Tacr1−/−↓Continuous[106]
NeurotensinNtsr1−/−↑Continuous[107]
Ntsr2−/−↑Continuous[108]
  1. In the third column, symbols ≈, ↓, and ↑ indicate no significant difference, decreased, or increased alcohol intake and/or preference, respectively, in mutant versus control animals. Mice were tested unless when otherwise stated (rats); continuous, 24-h two-bottle choice alcohol consumption paradigm or 24-h progressive two-bottle free-choice alcohol consumption paradigm; DID, drinking in the dark; intermittent access, intermittent access two-bottle choice paradigm; limited, limited access procedures; Self-administration, operant alcohol self-administration; 4 bottles, four-bottle choice paradigm
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