Table 1.

Summarized effects of pharmacological manipulations of CRF/urocortin targets on alcohol-drinking studies.

Receptor	Mechanism	Drug	Drug administration	Results	Reference
CRFR1	Antagonist	Antalarmin	ip	Reduced escalateda drinking	Lodge and Lawrence (71), Cippitelli et al. (72), Hansson et al. (70), Chu et al. (75), Marinelli et al. (80), Lowery-Gionta et al. (73)
				Reduced ethanol seeking	Marinelli et al. (80), Funk et al. (81)
				No effect on escalateda drinking	Yang et al. (79), Molander et al. (78)
			Into CeA	Reduced escalateda drinking	Lowery-Gionta et al. (73)
CRFR1	Antagonist	CP-154,526	ip	Reduced stress-induced reinstatement of ethanol seeking	Le et al. (82)
				Reduced escalateda drinking	Correia et al. (83), Hwa et al. (84), Lowery et al. (85, 86), Overstreet et al. (87), Sparta et al. (76, 88)
			icv (chronic minipump)	No effect on escalateda drinking	Hwa et al. (84)
			Into VTA	Reduced escalateda drinking	Hwa et al. (74), Sparta et al. (89)
			Into DRN	Reduced escalateda drinking	Hwa et al. (74, 84)
			Into MRN	No effect on escalateda drinking	Hwa et al. (84)
CRFR1	Antagonist	CP 376,395	ip	Reduced escalateda drinking	Giardino and Ryabinin (77), Hwa et al. (84), Simms et al. (90)
			icv (chronic minipump)	Reduced escalateda drinking only on day 1; no effect in remaining days	Hwa et al. (84)
CRFR1	Antagonist	CRA-1000	ip	Reduced escalateda drinking	Overstreet et al. (87, 91), Lowery-Gionta et al. (73)
CRFR1	Antagonist	LWH-63	ip	Reduced escalateda drinking	Lowery-Gionta et al. (73)
			sc	Reduced escalateda drinking	Sabino et al. (92)
				Modestly increased limited access alcohol and water drinking	Sabino et al. (92)
CRFR1	Antagonist	MJL-1-109-2	ip	Reduced escalateda drinking	Funk et al. (81)
				No effect on drinking	Sabino et al. (92)
CRFR1	Antagonist	MPZP	sc	Reduced escalateda drinking	Gilpin et al. (93), Richardson et al. (94)
				No effect on escalateda drinking	Ji et al. (95)
CRFR1	Antagonist	MTIP	ip	Reduced stress-induced reinstatement of ethanol seeking	Gehlert et al. (96)
				Reduced escalateda drinking	Gehlert et al. (96)
CRFR1	Antagonist	NBI-27914	ip	Reduced escalateda drinking	Lowery-Gionta et al. (73), Giardino and Ryabinin (77)
CRFR1	Antagonist	NBI-27914	ip	No effect on escalateda drinking	Molander et al. (78)
CRFR1	Antagonist	R121919	ip	No effect on escalateda drinking	Yang et al. (79)
			sc	Increased escalateda drinking	Sabino et al. (92)
				Prevented stress-induced suppression of drinking	Sabino et al. (92)
				No effect on escalateda drinking	Sabino et al. (97)
				Reduced escalateda drinking	Funk et al. (81), Roberto et al. (24), Roltsch et al. (98)
CRFR1	Antagonist	SSR125543	Into NAcc	Reduced escalateda drinking	Knapp et al. (99)
			Into AMY, DRN	No effect on escalateda drinking	Knapp et al. (99)
CRFR1/2	Agonist	CRF	icv	No effect on escalateda drinking	O’Callaghan et al. (100)
				Reduced escalateda drinking	Bell et al. (101), Thorsell et al. (102)
				Reinstated CRF-induced ethanol seeking	Le et al. (103)
			Into DRN	No effect on drinking	Weitemier and Ryabinin (104)
			Into LS	Reduced escalateda drinking and water intake	Ryabinin et al. (105)
			Into MRN	Reinstated CRF-induced ethanol seeking	Le et al. (103)
			Into NAcc	Further augmented escalateda drinking	Knapp et al. (99)
CRFR1/2	Agonist	CRF	Into CeA, DRN, VTA, PVN	No effect on escalateda drinking	Knapp et al. (99)
CRFR1/2	Agonist	Ucn 1	Into DRN	No effect on drinking and reduced water intake	Weitemier and Ryabinin (104)
			Into LS	Reduced escalateda drinking	Ryabinin et al. (105)
CRFR1/2	Antagonist	d-Phe-CRF	icv	Reduced escalateda drinking	Valdez et al. (106)
				Reduced reinstatement of ethanol seeking induced by the combination of stress and ethanol-cues	Liu and Weiss (107)
				Reduced stress-induced reinstatement of ethanol seeking	Le et al. (82), Liu and Weiss (107)
				No effect on cue-induced reinstatement of ethanol seeking	Liu and Weiss (107)
			Into CeA	Reduced escalateda drinking	Finn et al. (108), Funk et al. (109, 110)
			Into MRN	Reduced yohimbine-induced reinstatement	Le et al. (111)
			Into MRN	Reduced stress-induced reinstatement	Le et al. (103)
CRFR1/2	Antagonist	Alpha-helical CRF	icv	Increased drinking in low preference animals	O’Callaghan et al. (100)
				Reduced escalateda drinking	Lowery et al. (86)
				No effect on drinking in high preference animals	O’Callaghan et al. (100)
CRFR2	Agonist	Ucn 3	icv	Reduced escalateda drinking	Sharpe and Phillips (112), Valdez et al. (113), Lowery et al. (86)
			Into CeA	Reduced escalateda drinking	Funk and Koob (114)
				Increased drinking in control animals	Funk and Koob (114)
CRFR2	Antagonist	Astressin-2B	Into VTA	Reduced escalateda drinking	Albrechet-Souza et al. (115)
			Into CeA	No effect on escalateda drinking	Albrechet-Souza et al. (115)
CRFR2	Antagonist	Antisauvagine-30	Into DRN	No effect on drinking	Weitemier and Ryabinin (104)
CRF-BP	Antagonist	CRF(6–33)	Into VTA	Reduced escalateda drinking	Albrechet-Souza et al. (115)
			Into CeA	No effect on escalateda drinking	Albrechet-Souza et al. (115)

^aEscalated drinking refers to ethanol intake that is above baseline or control levels, as observed in protocols of alcohol deprivation, “binge” drinking (as in drinking-in-the-dark protocol), intermittent/limited access conditions, withdrawal from ethanol vapor or liquid diet exposure, prolonged ethanol access conditions, etc.

ip, intraperitoneal; sc, subcutaneous; icv, intracerebroventricular; AMY, amygdala; CeA, central nucleus of the amygdala; BLA, basolateral amygdala; DRN, dorsal raphé nucleus; MRN, median raphé nucleus; PVN, paraventricular nucleus of the hypothalamus; VTA, ventral tegmental area; NAcc, nucleus accumbens; LS, lateral septum.