Orexins in the midline thalamus are involved in the expression of conditioned place aversion to morphine withdrawal

Li, Yonghui; Wang, Huiying; Qi, K. H.; Chen, Xiaoyu; Li, Sa; Song, Nan; Kirouac, Gilbert J.

doi:10.1016/j.physbeh.2010.10.006

Cited by 61 publications

(46 citation statements)

References 63 publications

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“…4B and 5B) where the responses on the inactive lever stayed low and unaffected. Therefore the present data, consistent with earlier published findings, suggest that injection of Orx-A/Hcrt-1, SB334867, and TCSOX229 into the pPVT at the doses range used do not induce any nonspecific locomotor effect and further suggest that Orx-A/Hcrt-1 act on the PVT to produce arousal independent of general locomotor activation (Li et al, 2009(Li et al, , 2010b(Li et al, , 2011Barson et al, 2015).…”

Section: Discussionsupporting

confidence: 92%

“…Behavioral procedure. 2010b) in 0.9% sodium chloride (Hospira, Lake Forest, IL) or a combination of 0.5 mg Orx-A/Hcrt-1 (i.e., the minimal dose able to induce cocaine-seeking behavior) and the Hcrt-r1 antagonist SB334867 (0, 5, 10, or 15 mg; Lilly Research Laboratories, Indianapolis, IN) (Li et al, 2011) in $99.5% dimethylsulfoxide (DMSO; Sigma Aldrich, St. Louis, MO) or the Hcrt-r2 antagonist TCSOX229 (Tocris Biosciences, Bristol, UK; 0, 5, 10, or 15 mg; Li et al, 2011) in 0.9% sodium chloride (saline; Hospira, Lake Forest, IL). Intra-pPVT microinjections were made using a microinfusion pump (Harvard 22 Syringe Pump, Holliston, MA) with injectors extending 3.5 mm beyond the guide cannula.…”

Section: Methodsmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

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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“…That said, the high doses of SB-334867 used in some of these studies and the compound's limited specificity suggest that blockade of OX 2 receptors may in fact have contributed to the results of these studies (Scammell and Winrow, 2011;Shoblock et al, 2011). Indeed, more recent experiments with OX 2 SORAs JNJ10397049 and (2S)-1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl) -3,3-dimethyl-2-[(4-pyridinylmethyl)amino]-1-butanone (TCSOX 2 29) argue for a direct role of OX 2 receptor signaling in drug behaviors involving ethanol and morphine (Li et al, 2011;Shoblock et al, 2011). Shoblock et al (2011) expound upon the potential for an OX 2 SORA that might provide treatment for addiction and also serve to treat the comorbid insomnia that often accompanies drug use and contributes to relapse.…”

Section: A Central Modulation Of Behavior and Physiology By Orexin Smentioning

confidence: 85%

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

et al. 2012

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“…Moreover, orexin signalling in PVT may generate an aversive motivational state [121][122][123] and antagonism of OX 2 R in PVT blocks conditioned place aversion produced by naloxone-precipitated morphine withdrawal [124]. In summary, increasing evidence supports a role for PVT in reinstatement of extinguished drug seeking.…”

Section: R In Pvt Hadmentioning

confidence: 92%

The hypothalamus and the neurobiology of drug seeking

Marchant

Millan

McNally

2011

Cell. Mol. Life Sci.

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The hypothalamus is a neural structure critical for expression of motivated behaviours that ensure survival of the individual and the species. It is a heterogeneous structure, generally recognised to have four distinct regions in the rostrocaudal axis (preoptic, supraoptic, tuberal and mammillary). The tuberal hypothalamus in particular has been implicated in the neural control of appetitive motivation, including feeding and drug seeking. Here we review the role of the tuberal hypothalamus in appetitive motivation. First, we review evidence that different regions of the hypothalamus exert opposing control over feeding. We then review evidence that a similar bi-directional regulation characterises hypothalamic contributions to drug seeking and reward seeking. Lateral regions of the dorsal tuberal hypothalamus are important for promoting reinstatement of drug seeking, whereas medial regions of the dorsal tuberal hypothalamus are important for inhibiting this drug seeking after extinction training. Finally, we review evidence that these different roles for medial versus lateral dorsal tuberal hypothalamus in promoting or preventing reinstatement of drug seeking are mediated, at least in part, by different populations of hypothalamic neurons as well as the neural circuits in which they are located.

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Orexins in the midline thalamus are involved in the expression of conditioned place aversion to morphine withdrawal

Cited by 61 publications

References 63 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

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

The hypothalamus and the neurobiology of drug seeking

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