Table 1.

Summary of articles addressing the role of ghrelin and GLP-1 signaling in alcohol and drug addiction

Ghrelin administration	→ Activates the mesolimbic dopamine system, specifically the cholinergic–dopaminergic reward link, in rodents	Jerlhag et al. [30]
		Abizaid et al. [32]
		Jerlhag et al. [31]
		Jerlhag [36]
		Jerlhag et al. [41]
		Quarta et al. [37]
		Jerlhag et al. [38]
		Jerlhag et al. [33]
	→ Causes a focal activation of a network including ventral tegmental area, nucleus accumbens and lateral hypothalamus in rats	Wellman et al. [39]
	→ Increases novelty seeking in rats	Hansson et al. [50]
	→ Increases alcohol intake in mice when administered into the third ventricle, ventral tegmental area or laterodorsal tegmental area	Jerlhag et al. [55]
	→ Slightly increases alcohol intake in alcohol naïve rats when administered peripherally	Lyons et al. [61]
	→ Augments cocaine-induced hyperlocomotion and conditioned place preference in rats	Wellman et al. [86]
		Davis et al. [87]
	→ Increases the response in reward-related areas, such as nucleus accumbens, to food in humans	Malik et al. [40]
	→ Increases alcohol craving in alcohol dependent heavy-drinking individuals when injected intravenously	Leggio et al. [82]
Ghrelin knockout mice	→ Display attenuation of alcohol-induced reward as measured by locomotor stimulation, conditioned place preference and accumbal dopamine release	Jerlhag et al. [60]
		Bahi et al. [57]
Prevention of ghrelin penetration into the brain	→ Does not alter the rewarding properties of alcohol or alcohol intake in rodents	Jerlhag et al. [62]
Plasma levels of ghrelin	→ Are not different in high- and low-alcohol preferring rats	Landgren et al. [56]
	→ Are lower in high-alcohol preferring rats than in low-alcohol preferring rats	Szulc et al. [77]
	→ Are reduced by acute oral alcohol consumption in healthy volunteers	Calissendorff et al. [69]
		Calissendorff et al. [70]
		Zimmerman et al. [71]
	→ Which are increased by fasting are suppressed by acute intravenous administration of alcohol in healthy nonsmoking social drinkers	Leggio et al. [73]
	→ Are suppressed in active drinking in alcohol-dependent individuals	Addolorato et al. [74]
		Kraus et al. [76]
		Badaoui et al. [75]
	→ Are increased in abstinent alcoholics	Kim et al. [78]
		Kraus et al. [76]
		Wurst et al. [79]
	→ Are higher in alcohol dependent individuals with high craving scores than in those with low craving scores	Addolorato et al. [74]
		Wurst et al. [79]
		Koopmann et al. [80]
		Leggio et al. [81]
	→ Are increased in rats with high reinstatement of cocaine-seeking behavior	Tessari et al. [88]
Polymorphisms in ghrelin related genes	→ Are associated with high alcohol intake, personality traits important for alcohol dependence as well as with type II alcoholism	Landgren et al. [83]
		Landgren et al. [84]
		Landgren et al. [85]
	→ Are associated with smoking as well as with amphetamine dependence in humans	Landgren et al. [84]
		Suchankova et al. [95]
	→ Are associated with high sucrose intake	Landgren et al. [68]
“Ghrelin receptor” (GHS-R1A) antagonist treatment	→ Blocks the rewarding properties of alcohol in mice when administered centrally or peripherally	Jerlhag et al. [55]
	→ Decreases alcohol intake in rodents	Jerlhag et al. [55]
		Kaur and Ryabinin [58]
		Landgren et al. [56]
		Bahi et al. [57]
		Suchankova et al. [59]
	→ Decreases the motivation to consume alcohol as well as prevents relapse to alcohol drinking in rats	Landgren et al. [56]
	→ Blocks the rewarding properties of amphetamine, cocaine or nicotine in rodents	Jerlhag et al. [89]
		Abizaid et al. [91]
		Clifford et al. [90]
		Wellman et al. [94]
Ghrelin receptor (GHS-R1A) knockout mice	→ Display attenuation of the rewarding properties of alcohol as measured by locomotor stimulation, accumbal dopamine release as well as conditioned place preference	Jerlhag et al. [55]
	→ Display a reduction in cocaine-induced locomotor stimulation and sensitization	Clifford et al. [90]
		Abizaid et al. [91]
Ghrelin receptor (GHS-R1A) expression	→ Is detected in the nucleus accumbens, amygdala as well as on dopaminergic neurons in the ventral tegmental area and on cholinergic neurons in the laterodorsal tegmental area in rats	Abizaid et al. [32]
		Dickson et al. [34]
		Landgren et al. [23]
		Cruz et al. [66]
	→ Is altered in the ventral tegmental area following voluntary oral alcohol intake (3 or 10 months)	Landgren et al. [23]
		Suchankova et al. [59]
Administration of GLP-1 analogues	→ Decrease alcohol intake, alcohol seeking behavior and alcohol-induced reward in rodents	Egecioglu et al. [112]
		Shirazi et al. [113]
	→ Attenuate the rewarding properties of amphetamine and cocaine in rodents	Erreger et al. [115]
		Graham et al. [116]
		Egecioglu et al. [117]
	→ Prevent nicotine reward as well as block nicotine-induced expression of locomotor sensitization in mice	Egecioglu et al. [118]