Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat

Sato-Suzuki, Ikuko; Kita, Ichiro; Seki, Yoldaş; Oguri, Mitsugu; Arita, Hideho

doi:10.1016/s0166-4328(01)00307-2

Cited by 45 publications

(27 citation statements)

References 24 publications

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“…Most neurons in the PVT are sensitive to Orx-A/Hcrt-1 and Orx-B/Hcrt-2, and the prefrontal cortex is an important target of Orx/Hcrt-activated PVT neurons (Ishibashi et al, 2005;Huang et al, 2006). The present results suggest that Orx/Hcrt inputs to the PVT facilitate cortical activation that is linked to general arousal (Sato-Suzuki et al, 2002), which could explain the reinstatement of cocaine seeking. Moreover, Orx-A/Hcrt-1 administration in the PVT significantly increased dopamine levels in the nucleus accumbens (Choi et al, 2012), suggesting that the PVT is a key relay for Orx/Hcrt's effects on the mesolimbic dopamine system and reward-seeking behavior.…”

Section: Discussionmentioning

confidence: 50%

Orexin-A/Hypocretin-1 Mediates Cocaine-Seeking Behavior in the Posterior Paraventricular Nucleus of the Thalamus via Orexin/Hypocretin Receptor-2

Matzeu

Kerr

Weiss

et al. 2016

J Pharmacol Exp Ther

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Orexin/hypocretin (Orx/Hcrt) projections from the lateral hypothalamus to the paraventricular nucleus of the thalamus (PVT) are implicated in drug addiction. Specifically, the posterior section of the PVT (pPVT) innervates brain structures that modulate motivated behavior. This study investigated the role of pPVTOrx/Hcrt transmission in cocaine-seeking behavior. Because the effects of Orx/Hcrt are mediated by two Orx/Hcrt receptors (Hcrt-r1 and Hcrt-r2), we examined the extent to which Hcrt-r1 and Hcrt-r2 are involved in Orx/Hcrt-induced cocaine seeking. Male Wistar rats were made cocaine dependent by selfadministering cocaine 6 hours/day (long access) for 21 days. After self-administration training, the rats underwent daily extinction training, during which cocaine was withheld. After extinction, the rats were injected into the pPVT with Orx-A/Hcrt-1 (0-2 mg) alone or, using a single dose of 0.5 mg, in combination with an Hcrt-r1 antagonist (SB334867; 0-15 mg) or an Hcrt-r2 antagonist (TCSOX229; 0-15 mg). Orx-A/Hcrt-1 alone reinstated (primed) cocaine seeking. Unexpectedly, coadministration of Orx-A/Hcrt-1 with SB334867 did not have any effects on Orx-A/Hcrt-1-induced reinstatement, whereas when coadministered with Orx-A/Hcrt-1, TCSOX229 prevented cocaine-seeking behavior. These results indicate that Hcrt-r2 in the pPVT mediates the reinstating effect of Orx-A/Hcrt-1 in animals with a history of cocaine dependence and further identify Hcrt-r2 as a possible molecular target that can guide future therapeutic approaches for the prevention of drug-seeking behavior.

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Section: Discussionmentioning

confidence: 50%

Orexin-A/Hypocretin-1 Mediates Cocaine-Seeking Behavior in the Posterior Paraventricular Nucleus of the Thalamus via Orexin/Hypocretin Receptor-2

Matzeu

Kerr

Weiss

et al. 2016

J Pharmacol Exp Ther

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“…Orexin-containing neurons innervate forebrain and brain stem structures that are implicated in arousal (40,60). Orexins stimulate wakefulness when injected intracerebroventricularly (15) or into the lateral POA, PVN, TMN, or locus coeruleus (2,18,29,48). Orexinergic neurons discharge during active wakefulness, and they are silent in slow-wave sleep (25,30).…”

Section: Discussionmentioning

confidence: 99%

“…Lesion of the PVN decreases REMS sleep and abolishes the circadian sleep-wake cycles (42). Microinjections of orexin (48) or histamine (50) into the PVN elicit arousal responses. The PVN is also one of the major targets for ghrelin to induce feeding; injections of ghrelin induce c-fos expression in the PVN (36) and stimulate eating (65).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Szentirmai¹,

Kapás²,

Krueger³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

110

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Szentirmai É , Kapás L, Krueger JM. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Am J Physiol Regul Integr Comp Physiol 292: R575-R585, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00448.2006.-Ghrelin, a gutbrain peptide, is best known for its role in the stimulation of feeding and growth hormone release. In the brain, orexin, neuropeptide Y (NPY), and ghrelin are parts of a food intake regulatory circuit. Orexin and NPY are also implicated in maintaining wakefulness. Previous experiments in our laboratory revealed that intracerebroventricular injections of ghrelin induce wakefulness in rats. To further elucidate the possible role of ghrelin in the regulation of arousal, we studied the effects of microinjections of ghrelin into hypothalamic sites, which are implicated in the regulation of feeding and sleep, such as the lateral hypothalamus (LH), medial preoptic area (MPA), and paraventricular nucleus (PVN) on sleep in rats. Sleep responses, motor activity, and food intake after central administration of 0.04, 0.2, or 1 g (12, 60, or 300 pmol) ghrelin were recorded. Microinjections of ghrelin into the LH had strong wakefulness-promoting effects lasting for 2 h. Wakefulness was also stimulated by ghrelin injection into the MPA and PVN; the effects were confined to the first hour after the injection. Ghrelin's non-rapid-eye-movement sleepsuppressive effect was accompanied by attenuation in the electroencephalographic (EEG) slow-wave activity and changes in the EEG power spectrum. Food consumption was significantly stimulated after microinjections of ghrelin into each hypothalamic site. Together, these results are consistent with the hypothesis that forebrain ghrelinergic mechanisms play a role in the regulation of vigilance, possibly through activating the components of the food intake-and arousalpromoting network formed by orexin and NPY. lateral hypothalamus; medial preoptic area; paraventricular nucleus; electroencephalogram; slow-wave activity; sleep GHRELIN IS A 28-AMINO ACID peptide produced by endocrine cells in the gastrointestinal system and by neurons in the central nervous system (21). Circulating ghrelin is derived mainly from the stomach (1). Plasma ghrelin levels inversely correlate with feeding; fasting increases, while food intake reduces, plasma ghrelin concentrations (7, 61). In the brain, ghrelin is produced by arcuate nucleus (ARC) neurons and by a distinct hypothalamic neuronal population in the internuclear region (6). Ghrelin's actions are mediated by the growth hormone secretagogue receptor (GHS-R) (21). GHS-R mRNA is widely distributed in the gastrointestinal tract, sensory vagus fibers, and the brain. Those hypothalamic nuclei that are implicated in the regulation of feeding and/or sleep-wake activity, such as the lateral hypothalamus (LH), paraventricular nucleus (PVN), ARC, dorsomedial hypothalamic nucleus, anteroventral preoptic nucleus, anterior hypothalamic area, suprachiasmatic nucleus, anterolateral hypothalamic nucleus, and the...

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“…In the majority of studies, central administration (intracerebroventricular or intracisternal) of extraphysiological doses of orexin peptides, particularly OX-A, acts to increase blood pressure and heart rate, although differences in experimental paradigms have also found unchanged or decreased cardiovascular parameters with orexin administration (Samson et al, 1999Shirasaka et al, 1999;Chen et al, 2000;White et al, 2006 ]OX-B and TCSOX 2 29 either partially or fully blocked the effects of exogenous orexins, suggesting that both receptor subtypes are involved (White et al, 2006;Samson et al, 2007;Huang et al, 2010). Direct administration to specific brain regions evoked either increases or decreases in blood pressure and heart rate, suggesting that stimulation of different structures may indeed differentially modulate cardiovascular function; however, differences in protocol, dose, and state of anesthesia probably also contribute to the disparate results (Chen et al, 2000;Antunes et al, 2001;Machado et al, 2002;Sato-Suzuki et al, 2002;Smith et al, 2002Smith et al, , 2007de Oliveira et al, 2003;Shahid et al, 2011). In fact, the doses used in several of the studies is relatively high compared with the endogenous OX-A levels (0.2-0.4 pmol/ml) in rat CSF , and so the relevance to the role of intrinsic orexins in cardiovascular function is unknown.…”

Section: B Orexin Influences On Peripheral Physiologymentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

et al. 2012

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Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat

Cited by 45 publications

References 24 publications

Orexin-A/Hypocretin-1 Mediates Cocaine-Seeking Behavior in the Posterior Paraventricular Nucleus of the Thalamus via Orexin/Hypocretin Receptor-2

Orexin-A/Hypocretin-1 Mediates Cocaine-Seeking Behavior in the Posterior Paraventricular Nucleus of the Thalamus via Orexin/Hypocretin Receptor-2

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

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