PMC:4195273 / 57413-60289
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4195273","sourcedb":"PMC","sourceid":"4195273","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4195273","text":"The discrepancy between the anorexic effects of CART when injected i.c.v. vs. the predominately orexigenic effects of CART when delivered into specific hypothalamic nuclei suggests that CART expression/function in other brain areas may also be important to the regulation of food intake and energy homeostasis, also suggesting that CART may be involved in both anorexigenic and orexigenic circuits in the CNS (Parker and Bloom, 2012). Other potential areas for CART-mediated anorexic effects include the striatum, which is known to have upregulated CART expression following acute i.p. administration of psychostimulants (Douglass et al., 1995; Fagergren and Hurd, 1999; Hubert and Kuhar, 2008), reduced CART mRNA levels following fasting (Kristensen et al., 1998; Adams et al., 1999; Yang and Shieh, 2005), and has been shown to be involved in the mediation of reward and reinforcement (Koob and Bloom, 1988; Salamone, 1996; Upadhya et al., 2012) as well as the neuronal circuits controlling feeding behavior (Bakshi and Kelley, 1993; Gilbert and Cooper, 1995; Pothos et al., 1995; Stratford et al., 1997; Stratford and Kelley, 1999; Baldo et al., 2002; Yang and Shieh, 2005; Upadhya et al., 2012). Evidence for such a role was gained from experiments in a strain of CCK-1 receptor-deficient obese rats, where a significant reduction in CART immunoreactivity in the Arc was found potentially associated with a diminished anorectic effect of CART peptide compared to lean controls (Abraham et al., 2009). Furthermore, intra-accumbal CART peptide injection has been demonstrated to diminish both basal food consumption and food deprivation-induced feeding (Yang and Shieh, 2005; Jean et al., 2007), as well as potently attenuating the orexigenic effects of the GABA-A agonist muscimol (Yang and Shieh, 2005), albeit some inconsistency across different studies (Jaworski et al., 2008) (Table 1). The antagonistic effects of the GABA system and CART at the Acb were also demonstrated in the neurochemical phenotypes of hypothalamic neurons after the appetite-inducing microinjection of muscimol into the AcbSh, which increased Fos expression in orexin neurons at the perifornical area and NPY neurons at the Arc, while inhibiting that in Arc CART/POMC neurons (Zheng et al., 2003). In a recent study, subcutaneous injection of the GABA-A active neurosteroid ALLO significantly reduced CART immunoreactive cells and fibers in the AcbSh, as well as in other feeding-related hypothalamic nuclei such as the PVN, Arc and LHA (Nakhate et al., 2013). Direct CART administration into the Acb performed by an independent group generated no detectable influence on food reward assessed by food self-administration, yet triggered inhibitory effects on cocaine self-administration, an alternative measure of reward and reinforcement entailing dopaminergic functions (Jaworski et al., 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