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.
a  Cerebral aqueduct occlusion to interrupt forebrain-hindbrain CSF flow.
b  Inhibition 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.
c  Inhibition 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.
d  Acute administration through repeated injections and chronic overexpression using stereotactically targeted gene transfer.
e  Chronic 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).
g  Induction of Fos expression in the PVN, DMH, SON and Arc (hypothalamus), central nucleus of amygdala (cerebrum), PBN and NTS (hindbrain).
h  Induction of Fos expression in NTS neurons.
i  ↑ UCP-1 expression thermogenic capacity in BAT.