Archival ReportDysregulation of the Mesolimbic Dopamine System and Reward in MCH−/− Mice
Section snippets
Animals
The MCH−/− and MCH+/+ littermates were bred under our direction at Taconic (Hudson, New York). The MCH−/− mice were originally generated by the Maratos-Flier group, and the physiology of these mice has been characterized (7, 13). Mice used in this study had been backcrossed onto the C57BL6 background for at least 15 generations. Colonies are maintained as het × het breeders, progeny is genotyped, and MCH+/+ and MCH−/− animals were shipped to us and individually housed in the Beth Israel
MCHR1 Is Highly Expressed in the Ventral Striatum But Not in the Ventral Tegmental Area
Expression of MCHR1 in mouse brain was determined by in situ hybridization of antisense riboprobe according to published procedures (25). A strong signal was detected in the terminal regions of dopaminergic projections from the midbrain, especially in the ventral striatum, Acb, and the olfactory tubercle (Tu) (Figures 1A and 1B). The PFC and prelimbic (PrL) and infralimbic (IL) cortex showed intermediate levels of MCHR1 expression. More caudally, expression increased in the medial shell of the
Discussion
Food intake is a complex behavior requiring integration of both homeostatic and hedonic inputs (34). Homeostatic signals provide information on energy status, whereas hedonic inputs mediate the rewarding aspects of feeding. Both inputs are essential, because animals must both perceive hunger and in consequence engage in activities that result in finding and consuming a meal. Furthermore, recent reports describe effects of peptides such as leptin (35, 36) and ghrelin (37) on dopaminergic
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Actions of feeding-related peptides on the mesolimbic dopamine system in regulation of natural and drug rewards
2022, Addiction NeuroscienceRole of melanin-concentrating hormone in drug use disorders
2020, Brain ResearchConditional deletion of melanin-concentrating hormone receptor 1 from GABAergic neurons increases locomotor activity
2019, Molecular MetabolismCitation Excerpt :Results from whole animals are also consistent with increased dopaminergic tone. MCH- and MCHR1-deficient mice display enhanced sensitization to psychostimulants like amphetamine [11,17,19] and cocaine [20,42], as well as increased locomotor responses to the dopamine reuptake blocker GBR12909 [11,20]. We found that in addition to recapitulating the hyperactivity in global MCH- or MCHR-deficient mice, MCHR1 deletion from vGAT neurons in our mice also increased dopaminergic tone, and they were more sensitive to the hyperlocomotor effects of GBR12909.
Diversity in the lateral hypothalamic input to the ventral tegmental area
2019, NeuropharmacologyCitation Excerpt :Leptin's effects on VTA projecting LHMCH neurons were attenuated by diet-induced obesity and by fasting (Liu et al., 2017), suggesting that synaptic input modulating VTA-projecting LHMCH neurons is sensitive to energy fluxes. While it is unclear if the LHMCH projection to the VTA can modulate mesolimbic dopamine release in the NAc, it is likely that LHMCH can alter dopaminergic neurons through activity at terminals in the NAc or on medium spiny neurons, where high levels of MCH receptors are expressed (Brown et al., 2015; Chee et al., 2013; Pissios et al., 2008; Saito et al., 2001). Indeed, LHMCH projections to the NAc modulate appetitive behaviour (Georgescu et al., 2005).
Translating Animal Models of Obesity and Diabetes to the Clinic
2019, Handbook of Behavioral NeuroscienceHypothalamic neuropeptide signaling in alcohol addiction
2016, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :In contrast to the reward-promoting effects of GAL, ENK, and OX, the ability of MCH to promote alcohol drinking may be due to its induction of dysphoria. Mice lacking the MCHR1 show greater evoked DA release from the NAc shell (Pissios et al., 2008), suggesting that activation of the MCHR1 normally inhibits these levels. Moreover, hypothalamic MCH gene expression positively correlates with aversive responses, including conditioned taste aversion (Mitra et al., 2012) and immobility in a forced swim test (Garcia-Fuster et al., 2012).