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 carrierContinuous[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/AAContinuous[78]
Grm5AA/AADID[78]
Grm5AA/AASelf-administration[78]
Grm2−/−↑ (only at high concentrations)Continuous[79]
Grm4−/−Continuous[80]
B6.129/Ola−Grm7tmNovartisContinuous[81]
CRFCrhr1−/−Continuous[82]
Crhr1−/−Stress + continuous[82]
CRF1NestinCreContinuous[83]
Crhr1−/−Continuous[83]
CRF1NestinCreStress + 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