Table 1.

Summary of the metabolic and behavioral effects of central CART administration via various intracerebroventricular and intranuclear delivery methods.

Year	Publication	Targeting peptide/CART fragment	Route of adminis-tration	Species (genetic background)	Diet	Feeding behavior and body weight alterations	Locomotor behavior
1998	Kristensen et al., 1998	CART I (55–102)	i.c.v.	Rat	Standard chow	↓ Spontaneous feeding; ↓ Fast-induced feeding; ↓ NPY-induced feeding	N/A
1998	Lambert et al., 1998	CART (55–59)	i.c.v.	Rat	Standard chow	~ Spontaneous feeding	N/A
1998	Lambert et al., 1998	CART (55–76)	i.c.v.	Rat	Standard chow	↓ Spontaneous feeding; ↓ NPY-induced feeding	N/A
1998	Lambert et al., 1998	CART (62–76)	i.c.v.	Rat	Standard chow	↓ Spontaneous feeding	N/A
1998	Thim et al., 1998	CART I (55–102); CART II (62–102)	i.c.v.	Mouse	Standard chow	↓ Fast-induced feeding	N/A
1999	Vrang et al., 1999b	CART I (42–89)	i.c.v.g	Rat	Standard chow	↓ Spontaneous feeding (in food-restricted animals) and ↓ NPY-induced feeding	N/A
2000	Edwards et al., 2000	CART I (55–102)	i.c.v.	Rat	Standard chow	↓ Spontaneous feeding	N/A
2000	Kask et al., 2000	CART (62–76)	i.c.v.	Rat	Standard chow	↓ Spontaneous feeding	N/A
2000	Volkoff and Peter, 2000	CART I (55–102); CART (62–76)	i.c.v.	Goldfish	Standard chow	↓ Spontaneous feeding and ↓ NPY-induced feeding (in food-restricted animals)	N/A
2000	Larsen et al., 2000	CART I (42–89)	i.c.v. (chronic infusion)	Lean and obese Zucker (fa/fa) rats	Standard chow	↓ Spontaneous feeding (in both free-feeding and food-restricted animals); dose-dependent ↓ in body weight	Dose-dependent motor disturbances (combined gait and walking ataxia)
2000	Okumura et al., 2000	CART I (55–102)	i.c.	Rat	Standard chow	↓ Fast-induced feedingb	N/A
2000	Wang et al., 2000	CART I (55–102)	intra-PVN	Rat	Standard chow	↓ NPY-induced feedingi	N/A
2001	Bannon et al., 2001	CART I (55–102); CART II (62–102)	i.c.v.	Mouse	Standard chow	↓ Fast-induced feeding	N/A
2001	Abbott et al., 2001	CART I (55–102)	Hypothalamic intranuclear injections (VMH, Arc, PVN, SON, DMH, LHA and AHA)	Rat	Standard chow	↑ Spontaneous feeding (only measured in satiated animals cannulated into the DMH or Arc); ↑ Fast-induced feeding	N/A
2001	Abbott et al., 2001	CART I (55–102)	i.c.v. (3V)	Rat	Standard chow	↓ Spontaneous feeding; ↓ Fast-induced feeding (↓ feeding episodes)	Behavioral abnormalities marked by reduced feeding episodes, flat-backed posture and movement-associated tremors (behavioral analysis performed for 24-h fasted animals only but not satiated animals)
2001	Zheng et al., 2001	CART I (55–102)	i.c.v. (LV and 4V)	Rat	Sucrose solution or standard chow	↓ Spontaneous feeding (↓ short-term sucrose intake and ↓ overnight chow intake)—effects more pronounced in 4V compared to LV administration	Alterations in motor behavior (mild movement-associated tremors in part of 4V injected subjects)
2001a	Aja et al., 2001a	CART I (55–102)	i.c.v.	Rat	Ensure liquid diet	↓ Spontaneous feeding (↓ liquid diet intake in licks and meal size in food restricted animals)	Altered oral motor function and behavioral alterations (trance-like state, flat-backed and arched-backed postures, cage licking, movement-associated tremors)
2001b	Aja et al., 2001b	CART I (55–102)	i.c.v. (3V)	Rat	Ensure liquid diet	↓ Spontaneous feeding (↓ liquid diet intake and observations of feeding in food restricted animals)—reductions significantly attentuated by aqueduct obstructiona	Alterations in motor behavior (flat-backed and arched-backed postures and movement-associated tremors)—alterations significantly attentuated by aqueduct obstructiona
2001b	Aja et al., 2001b	CART I (55–102)	i.c.v. (4V)	Rat	Ensure liquid diet	↓ Spontaneous feeding (↓ liquid diet intake and observations of feeding in food restricted animals)—reductions unaffected by aqueduct obstructiona	Alterations in motor behavior (flat-backed and arched-backed postures and movement-associated tremors)—alterations unaffected by aqueduct obstructiona
2002	Aja et al., 2002	CART I (55–102)	i.c.v. (4V)	Rat	Ensure liquid diet	↓ Spontaneous feeding (↓ liquid diet and water intake in food restricted animals); production of conditioned taste aversion	N/A
2002	Rohner-Jeanrenaud et al., 2002	CART I (55–102)	i.c.v. (chronic infusion)	Rat (normal and DIO)	Standard chow or HFD	↓ Spontaneous feeding and ↓ NPY-induced feeding; ↓ body weight gain	N/A
2002	Zheng et al., 2002	CART I (55–102)	i.c.v. (4V)h and intra-NTS	Rat	Sucrose solution or standard chow	↓ Spontaneous feeding (↓ short-term sucrose intake)—effects more pronounced in 4V compared to intra-NTS administration	N/A
2003	Smedh and Moran, 2003	CART I (55–102)	i.c.v. (4V)	Rat	Sucrose solution	↓ Spontaneous feeding (↓ sucrose intake in food restricted animals); altered lick microstrcuture parametersc	N/A
2003	Kong et al., 2003	CART I (55–102)	intra-Arcd	Rat	Standard chow	↑ Spontaneous feeding (in both free-feeding and food-restricted animals) and ↑ Fast-induced feeding; ↑ cumulative body weight gain; ↑ body weight loss following 24-hr fasting and food restrictioni	N/A
2004	Wortley et al., 2004	CART I (55–102)	i.c.v. (3V)	Rat	Standard chow	↓ Spontaneous feeding	N/A
2005	Yang et al., 2005	CART I (55–102)	intra-AcbSh	Rat	Standard chow	↓ Spontaneous feeding; ↓ Fast-induced feeding; ↓ GABA-A agonist muscimol-induced feeding	N/A
2007	Qing and Chen, 2007	rat CART cDNA	i.c.v.e	Rat (DIO)	High fat/high sucrose diet	↓ Spontaneous feeding; ↓ Fast-induced feeding; ↓ body weight gain (↓ lean mass; fat mass unaffected)	N/A
2007	Jean et al., 2007	CART I (55–102)	intra-AcbSh	Mouse	Standard chow	↓ Fast-induced feeding	N/A
2007	Jean et al., 2007	CART siRNA	intra-AcbSh	Mouse	Standard chow	↑ Spontaneous feeding and ↓ stimulating 5-HT4R- or MDMA-induced anorexia in staved animals	N/A
2008	Smith et al., 2008	rAAV encoding full length rat CART cDNA (GenBank accession no. U10071)	intra-PVNe	Rat	Standard chow or HFD	↑ Cumulative feeding and cumulative body weight gain; effects more accentuated on HFD	N/A
2009	Skibicka et al., 2009	CART I (55–102)	i.c.v. (4V) or intra-NTS	Rat	Standard chow	[4V injection]f ↓ Spontaneous feeding and body weight (in food-restricted animals); hypophagic response and weight loss attenuated by pre-treatment with hindbrain delivery of GLP-1R antagonist (exendin-9-39); intra-NTS injection produced no observable effect on feeding or body weight	N/A
2010	Hou et al., 2010	CART I (55–102)	intra-Arc; intra-DMH	Streptozotocin-diabetic rats	Standard chow or HFD	Chow diet: ↑ Spontaneous feeding (in satiated animals) (Arc) and ↑ Fast-induced feeding (DMH and Arc); HFD: ↑ Spontaneous feeding (Arc)	N/A
2011	Nakhate et al., 2011	CART I (54–102)	i.c.v.	Rat	Standard chow	↓ Spontaneous feeding and body weight; attenuated social isolation-induced hyperphagia and body weight gain	N/A
2013	Nakhate et al., 2013	CART I (54–102)	i.c.v.	Rat	Standard chow	↓ Spontaneous feeding; attenuated ALLO-induced hyperphagia and weight gain; potentiated DHEAS-induced anorexia and weight loss	N/A

CSF, cerebrospinal fluid; DIO, diet-induced obese; HFD, high fat diet; BAT, brown adipose tissue; i.c.v., intracerebroventricular; i.c., intracisternal; LV, lateral ventricle; 3V, third ventricle; 4V, fourth ventricle; Acb, nucleus accumbens; AcbSh, nucleus accumbens shell; AHA, anterior hypothalamic area; Arc, arcuate nucleus; DMH, dorsomedial nucleus; LHA, lateral hypothalamic area; NTS, nucleus of the solitary tract; PBN, parabrachial nucleus; PVN, paraventricular nucleus; SON, supraoptic nucleus; VMH, ventromedial hypothalamic nucleus.

Effects on body weight described where results presented, otherwise either unaffected or information unavailable.

Effects on locomotor behavior described where results presented, otherwise either unaffected or information unavailable.

^aCerebral aqueduct occlusion to interrupt forebrain-hindbrain CSF flow.

^bInhibition of gastric function (suppression of gastric acid secretion and gastric emptying); inhibition of gastric acid secretion remained in vagotomized animals; inhibition of gastric acid secretion blocked by pretreatment with central administration of CRF receptor antagonist α-helical CRF9-41.

^cInhibition of gastric function (suppression of gastric emptying); inhibition of gastric emptying blocked by pretreatment with central administration of CRF receptor antagonist α-helical CRF9-41; CART-induced inhibition of gastric emptying proposed unlikely to contribute to CART-mediated inhibition of food intake.

^dAcute administration through repeated injections and chronic overexpression using stereotactically targeted gene transfer.

^eChronic overexpression using recombinant adeno-associated virus vector containing rat CART cDNA.

^f↑ Blood glucose levels; hyperglycemic response not altered by GLP-1R blockade in animals pre-treated with GLP-1R antagonist (exendin-9-39).

^gInduction of Fos expression in the PVN, DMH, SON and Arc (hypothalamus), central nucleus of amygdala (cerebrum), PBN and NTS (hindbrain).

^hInduction of Fos expression in NTS neurons.

ⁱ↑ UCP-1 expression thermogenic capacity in BAT.