GABAA receptors mediate orexin-A induced stimulation of food intake

Kokare, Dadasaheb M.; Patole, Angad M.; Carta, Anna R.; Chopde, Chandrabhan T.; Subhedar, Nishikant K.

doi:10.1016/j.neuropharm.2005.07.019

Cited by 36 publications

(16 citation statements)

References 62 publications

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“…CB1 receptors are expressed in GABA neurons in the rat telencephalon [18] ; consequently, cannabinoids can control GABAergic transmission in several prosencephalic regions [19] . Moreover, CB1 activation results in inhibition of GABA release [20] , and it has been suggested recently that the hyperphagic effect of orexin A could be mediated by modulation of GABA-A receptor activity [21] . However, the reinforcing value of food is also mediated by dopaminergic activity [22] , and it has been proposed that low brain dopamine activity in obese subjects could predispose them to excessive use of food [23] .…”

Section: Discussionmentioning

confidence: 99%

Type 1 Diabetes Alters Brain Cannabinoid Receptor Expression and Phosphorylation Status in Rats

Díaz-Asensio

Setién²,

Echevarrı́a³

et al. 2008

Horm Metab Res

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One of the most common symptoms of diabetes is extreme hunger, but the brain mechanism underlying this hyperphagia is unknown. The endocannabinoid system has emerged as one of the main food intake regulators in the brain. However, the effects of type 1 diabetes on the endocannabinoid system are not completely known. Thus, the aim of the present work is to establish the possible alterations induced by type 1 diabetes on the brain endocannabinoid system in rats. Western blot and immunocytochemistry were used to measure CB1 and phosphorylated CB1 receptor expression in several prosencephalic regions in streptozotocin-induced type 1 diabetic rats. Serum leptin levels were measured by ELISA. CB1 receptor expression was increased in striatum and hypothalamus of diabetic animals, with no changes in other brain areas studied. CB1 receptor phosphorylation was also increased in the same brain areas. Type 1 diabetes induced significant weight loss, and serum leptin levels were severely decreased. These results reinforce the possible role of the CB1 receptor as a pharmacological target for the clinical management of appetite in diabetic patients.

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Section: Discussionmentioning

confidence: 99%

Type 1 Diabetes Alters Brain Cannabinoid Receptor Expression and Phosphorylation Status in Rats

Díaz-Asensio

Setién²,

Echevarrı́a³

et al. 2008

Horm Metab Res

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“…The details of this procedure and post-surgical care have already been described in our previous studies (Kokare et al, 2005(Kokare et al, , 2006. A stainless steel guide cannula (C316G/Spc; Plastics One, Roanoke, VA, USA) was implanted into the right lateral cerebral ventricle using the stereotaxic coordinates, −0.8 mm posterior, +1.3 mm lateral to midline and 3.5 mm ventral with respect to the bregma as per the stereotaxic atlas described by Paxinos and Watson (1998).…”

Section: Intracerebroventricular (Icv) Cannulationmentioning

confidence: 99%

“…The methods of icv injection, and the preparation of aCSF have already been described (Kokare et al, 2005(Kokare et al, , 2006. The rats in each group were administered each day, for four days in acquisition and immediately before retrieval, between 0900 and 1200 h. Fifteen minutes after being injected, individual rats were placed in the MWM for behavioral study.…”

Section: Drugs Administrationmentioning

confidence: 99%

Cocaine- and amphetamine-regulated transcript peptide increases spatial learning and memory in rats

et al. 2011

Self Cite

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“…This sheds light on the self-regulatory mechanism of Ox neurons via OX 1 R and OX 2 R auto-receptors. Previous studies have demonstrated the presence of inhibitory GABA B receptors on the Ox neurons [33], [75], [76], [77] and there is evidence that GABA A receptors are also present on Ox neurons (Backberg et al, 2004, Kokare et al, 2006). This could suggest a one-way relationship between GABAergic and Ox neurons wherein GABAergic neurons exerts an inhibitory effect on the Ox neurons under the partial DRN’s serotonergic control, consistent with Yamanaka et al (2010).…”

Section: Resultsmentioning

confidence: 98%

“…Other connections in the circuit based on other previous work: (viii) excitatory connection and receptor types are not known [82]; (ix) GABA A/B [33], [75], [76], [77]; (x) AMPAR [79] and NMDAR1 (found in the current study); (xi) GABA B [77]; (xiii) Ox 2 R [4], Ox 1 R and Ox 2 R (found in the current studies); (xv) 5-HT 1B/1D [34]; 5-HT 1A/2A/2C [69]; (xvi) 5-HT 7 [34]; (xvii) GABA A/B [34]; (xviii) AMPAR and NMDAR [34]; (xix) AMPAR and NMDAR [34]; (xxi) 5-HT 1A R [83]. For the connections (xii), (xiv), (xx) and (xxii) (shown by black dotted circle/arrow in Figure 10A), we implicitly assume that non-principal neurons (GABAergic and glutamatergic neurons in LHA and DRN) are self-coupled.…”

Section: Resultsmentioning

confidence: 99%

Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study

et al. 2014

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Orexinergic/hypocretinergic (Ox) neurotransmission plays an important role in regulating sleep, as well as in anxiety and depression, for which the serotonergic (5-HT) system is also involved in. However, little is known regarding the direct and indirect interactions between 5-HT in the dorsal raphe nucleus (DRN) and Ox neurons in the lateral hypothalamus (LHA). In this study, we report the additional presence of 5-HT1BR, 5-HT2AR, 5-HT2CR and fast ligand-gated 5-HT3AR subtypes on the Ox neurons of transgenic Ox-enhanced green fluorescent protein (Ox-EGFP) and wild type C57Bl/6 mice using single and double immunofluorescence (IF) staining, respectively, and quantify the colocalization for each 5-HT receptor subtype. We further reveal the presence of 5-HT3AR and 5-HT1AR on GABAergic neurons in LHA. We also identify NMDAR1, OX1R and OX2R on Ox neurons, but none on adjacent GABAergic neurons. This suggests a one-way relationship between LHA’s GABAergic and Ox neurons, wherein GABAergic neurons exerts an inhibitory effect on Ox neurons under partial DRN’s 5-HT control. We also show that Ox axonal projections receive glutamatergic (PSD-95 immunopositive) and GABAergic (Gephyrin immunopositive) inputs in the DRN. We consider these and other available findings into our computational model to explore possible effects of neural circuit connection types and timescales on the DRN-LHA system’s dynamics. We find that if the connections from 5-HT to LHA’s GABAergic neurons are weakly excitatory or inhibitory, the network exhibits slow oscillations; not observed when the connection is strongly excitatory. Furthermore, if Ox directly excites 5-HT neurons at a fast timescale, phasic Ox activation can lead to an increase in 5-HT activity; no significant effect with slower timescale. Overall, our experimental and computational approaches provide insights towards a more complete understanding of the complex relationship between 5-HT in the DRN and Ox in the LHA.

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GABAA receptors mediate orexin-A induced stimulation of food intake

Cited by 36 publications

References 62 publications

Type 1 Diabetes Alters Brain Cannabinoid Receptor Expression and Phosphorylation Status in Rats

Type 1 Diabetes Alters Brain Cannabinoid Receptor Expression and Phosphorylation Status in Rats

Cocaine- and amphetamine-regulated transcript peptide increases spatial learning and memory in rats

Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study

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