Anatomical substrates of orexin–dopamine interactions: lateral hypothalamic projections to the ventral tegmental area

Fadel, Jim R.; Deutch, Ariel Y.

doi:10.1016/s0306-4522(02)00017-9

Cited by 459 publications

(348 citation statements)

References 44 publications

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“…These studies demonstrate a robust and dose-dependent increase in DA efflux within the PFC, but not within Acc, following ICV-administered HCRT-1. HCRT fibers are located in close proximity to DA cell bodies in the VTA, a major source of PFC-and Accprojecting DA neurons (Fadel and Deutch, 2002;Baldo et al, 2003). To test the hypothesis that HCRT acts directly within the VTA to increase DA neurotransmission, we examined the effects of intra-VTA infusion of HCRT-1 on DA efflux within the PFC and Acc.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is possible that this subpopulation of DA neurons display a greater sensitivity to salient environmental stimuli and/or HCRT-1 than other, non-PFCprojecting, DA neurons. Finally, ICV infusion of HCRT may activate LH HCRT neurons via neighboring glutamatergic neurons (Li et al, 2002), which project both to VTA and PFC, but only sparsely to Acc (Fadel and Deutch, 2002).…”

Section: Circuitry Underlying Selective Increase In Da Efflux By Hcrtmentioning

confidence: 99%

“…Acting within the prefrontal cortex (PFC) and nucleus accumbens (Acc), dopamine (DA) exerts prominent modulatory actions on a variety of higher-level cognitive and affective processes (Ikemoto and Panksepp, 1999;SmithRoe and Kelley, 2000;Baldwin et al, 2002). Thus, it is of interest that HCRT fibers are found in close association with DA neurons located within the ventral tegmental area (VTA) and substantia nigra Fadel and Deutch, 2002;Baldo et al, 2003). Further, VTA and substantia nigra neurons express HCRT1 and HCRT2 receptor mRNA (Marcus et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area

Vittoz

Berridge

2005

Neuropsychopharmacol

164

113

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Hypocretins (HCRTs) modulate a variety of behavioral and physiological processes, in part via interactions with multiple ascending modulatory systems. Further, HCRT efferents from the lateral hypothalamus innervate midbrain dopamine (DA) nuclei, and DA cell bodies express HCRT receptors. Combined, these observations suggest that HCRT may influence behavioral state and/or statedependent processes via modulation of DA neurotransmission. The current studies used in vivo microdialysis in the unanesthetized rat to first characterize the effect of intracerebroventricular infusion of HCRT-1 (0.07, 0.7 nmol) on extracellular levels of DA within the prefrontal cortex (PFC) and nucleus accumbens (Acc). Electroencephalographic/electromyographic measures of sleep-wake state were collected along with select behavioral measures (eg locomotor activity, grooming). HCRT-1 dose-dependently increased PFC dialysate DA levels, and these increases were closely correlated with increases in time spent awake. In contrast, Acc DA levels were unaffected. Additional studies examined whether HCRT-1 acts directly within the ventral tegmental area (VTA) to selectively increase PFC DA efflux and modulate behavioral state. Unilateral infusion of HCRT-1 (0.1, 1.0 nmol) within the VTA increased PFC, but not Acc, DA levels. Importantly, intra-VTA infusion of HCRT-1 increased the time spent awake and grooming. Moreover, HCRT-induced increases in both time spent awake and time spent grooming were significantly correlated with post-infusion PFC DA levels. The current observations predict a prominent modulatory influence of HCRT on PFC-dependent cognitive and affective processes that results, in part, from actions within the VTA. Additionally, these observations suggest that the activation of VTA DA neurons contributes to the behavioral state-modulatory actions of HCRT.

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Section: Discussionmentioning

confidence: 99%

Section: Circuitry Underlying Selective Increase In Da Efflux By Hcrtmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area

Vittoz

Berridge

2005

Neuropsychopharmacol

164

113

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“…26 CB1 receptors are expressed in areas of the hypothalamus involved in appetite control, such as the paraventricular nucleus (PVN), where they are expressed in CRH-and CART-containing neurons, and in the lateral hypothalamus, where they are present in orexin-and melanin concentrating hormone (MCH)-containing neurons. 27 This latter site is of particular interest, as orexinand MCH neurons also express functional leptin receptors, 28,29 and they have dense projections to dopaminergic neurons in the ventral tegmental area, 30 where they modulate the mesolimbic dopaminergic pathway involved in food reward. Thus, they are a likely site for the proposed leptin/ endocannabinoid interaction in the control of food intake, 22 and could also represent a site of integration of hypothalamic and extrahypothalamic structures involved in the orexigenic effect of endocannabinoids.…”

Section: Endocannabinoid Regulation Of Appetitive Behaviormentioning

confidence: 99%

The role of the endocannabinoid system in the control of energy homeostasis

et al. 2006

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The endocannabinoid system has recently emerged as an important regulator of energy homeostasis, involved in the control of both appetite and peripheral fat metabolism. We briefly review current understanding of the possible sites of action and cellular mechanisms involved in the central appetitive and peripheral metabolic effects of endocannabinoids. Studies in our laboratory, using leptin-deficient obese rodents and CB1 cannabinoid receptor (CB1)-deficient mice, have indicated that endocannabinoids acting via CB1 are involved in the hunger-induced increase in food intake and are negatively regulated by leptin in brain areas involved in appetite control, including the hypothalamus, limbic forebrain and amygdala. CB1 À/À mice are lean and are resistant to diet-induced obesity (DIO) despite similar energy intake to wild-type mice with DIO, suggesting that CB1 regulation of body weight involves additional peripheral targets. Such targets appear to include both adipose tissue and the liver. CB1 expressed in adipocytes has been implicated in the control of adiponectin secretion and lipoprotein lipase activity. Recent findings indicate that both endocannabinoids and CB1 are present in the liver and are upregulated in DIO. CB1 stimulation increases de novo hepatic lipogenesis through activation of the fatty acid biosynthetic pathway. Components of this pathway are also expressed in the hypothalamus where they have been implicated in the regulation of appetite. The fatty acid biosynthetic pathway may thus represent a common molecular target for the central appetitive and peripheral metabolic effects of endocannabinoids.

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“…The orexin ligands, orexin A and orexin B, arise from the precursor peptide prepro-orexin by proteolytic processing (27,29) and activate the two G-protein coupled receptors, orexin 1 receptor (Ox1r) and orexin 2 receptor (Ox2r) (27). Interestingly, the orexin receptors and orexinergic projections from the hypothalamus are localized in regions previously shown to play a role in drug addiction, such as the VTA (26,(30)(31)(32), Acb, substantia nigra (26), and LC (33,34). Orexin neurons located in the LH innervate several regions along the trajectory of the mesocorticolimbic pathway (26,32).…”

Section: Introductionmentioning

confidence: 99%

Orexin Mediates the Expression of Precipitated Morphine Withdrawal and Concurrent Activation of the Nucleus Accumbens Shell

Sharf

Sarhan

DiLeone

2008

Biological Psychiatry

128

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Anatomical substrates of orexin–dopamine interactions: lateral hypothalamic projections to the ventral tegmental area

Cited by 459 publications

References 44 publications

Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area

Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area

The role of the endocannabinoid system in the control of energy homeostasis

Orexin Mediates the Expression of Precipitated Morphine Withdrawal and Concurrent Activation of the Nucleus Accumbens Shell

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