Role of glutamate ionotropic receptors in the dorsomedial hypothalamic nucleus on anxiety and locomotor behavior

Abstract Background Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals. Objective To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated. Methods c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.). Results Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part. Conclusion HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep–wake cycle by engaging the hypothalamus.

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The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation

Physiology & Behavior ◽

10.1016/s0031-9384(02)00756-4 ◽

2002 ◽

Vol 76 (3) ◽

pp. 431-442 ◽

Cited By ~ 144

Author(s):

Larry L. Bellinger ◽

Lee L. Bernardis

Keyword(s):

Body Weight ◽

Ingestive Behavior ◽

Hypothalamic Nucleus ◽

Weight Regulation ◽

Body Weight Regulation ◽

Dorsomedial Hypothalamic Nucleus

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The Dorsomedial Hypothalamic Nucleus Is Not Necessary for the Expression of Circadian Food-Anticipatory Activity in Rats

Journal of Biological Rhythms ◽

10.1177/0748730407307804 ◽

2007 ◽

Vol 22 (6) ◽

pp. 467-478 ◽

Cited By ~ 91

Author(s):

Glenn J. Landry ◽

Glenn R. Yamakawa ◽

Ian C. Webb ◽

Rhiannon J. Mear ◽

Ralph E. Mistlberger

Keyword(s):

Hypothalamic Nucleus ◽

Food Anticipatory Activity ◽

Dorsomedial Hypothalamic Nucleus ◽

Anticipatory Activity

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The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity

Nutrition & Metabolism ◽

10.1186/s12986-021-00582-z ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Yuko Maejima ◽

Shoko Yokota ◽

Masaru Shimizu ◽

Shoichiro Horita ◽

Daisuke Kobayashi ◽

...

Keyword(s):

Nucleus Tractus Solitarius ◽

Physiological Role ◽

Feeding Pattern ◽

Hypothalamic Nucleus ◽

Acid Decarboxylase ◽

Mrna Levels ◽

Dorsomedial Hypothalamic Nucleus ◽

Fos Expression ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Abstract Background Feeding rhythm disruption contributes to the development of obesity. The receptors of glucagon-like peptide-1 (GLP-1) are distributed in the wide regions of the brain. Among these regions, GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. However, the physiological roles of GLP-1R expressing neurons in the DMH remain elusive. Methods To examine the physiological role of GLP-1R expressing neurons in the DMH, saporin-conjugated exenatide4 was injected into rat brain DMH to delete GLP-1R-positive neurons. Subsequently, locomotor activity, diurnal feeding pattern, amount of food intake and body weight were measured. Results This deletion of GLP-1R-positive neurons in the DMH induced hyperphagia, the disruption of diurnal feeding pattern, and obesity. The deletion of GLP-1R expressing neurons also reduced glutamic acid decarboxylase 67 and cholecystokinin A receptor mRNA levels in the DMH. Also, it reduced the c-fos expression after refeeding in the suprachiasmatic nucleus (SCN). Thirty percent of DMH neurons projecting to the SCN expressed GLP-1R. Functionally, refeeding after fasting induced c-fos expression in the SCN projecting neurons in the DMH. As for the projection to the DMH, neurons in the nucleus tractus solitarius (NTS) were found to be projecting to the DMH, with 33% of those neurons being GLP-1-positive. Refeeding induced c-fos expression in the DMH projecting neurons in the NTS. Conclusion These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination. In addition, this meal signal may be transmitted to SCN neurons and change the neural activities.

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Injection of muscimol into posterior hypothalamus blocks stress-induced tachycardia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.257.1.r246 ◽

1989 ◽

Vol 257 (1) ◽

pp. R246-R251 ◽

Cited By ~ 3

Author(s):

M. Lisa ◽

E. Marmo ◽

J. H. Wible ◽

J. A. DiMicco

Keyword(s):

Gaba Receptors ◽

Potential Role ◽

Hypothalamic Nucleus ◽

Gamma Aminobutyric Acid ◽

Similar Treatment ◽

Cardiovascular Changes ◽

Vehicle Treatment ◽

Response To Stress ◽

Posterior Hypothalamic Nucleus

We have previously shown that the physiological and behavioral manifestations of emotional stress are produced when drugs impairing gamma-aminobutyric acid (GABA)-mediated synaptic inhibition are injected into the posterior hypothalamic nucleus in rats [Wible, J.H., Jr., F.C. Luft, and J.A. DiMicco. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R680-R687, 1988]. The purpose of this study was to assess further the potential role of GABA receptors in this region in the response to stress using muscimol, a GABAA receptor agonist. In six chronically instrumented conscious rats, air stress after vehicle treatment evoked marked and sustained tachycardia (+130 +/- 14 beats/min at +10 min) accompanied by a less dramatic increase in arterial pressure (+14 +/- 3 mmHg). Microinjection of muscimol (10 ng; 88 pmol) at the same posterior hypothalamic site in which GABA blockade causes cardiovascular changes similar to those seen in stress produced a modest depression of cardiovascular function in unstressed animals (-28 +/- 5 beats/min and -6 +/- 3 mmHg). However, similar treatment with muscimol virtually abolished the stress-induced tachycardia in the same rats (+9 +/- 8 beats/min), while having no significant effect on baroreflex-evoked increases in heart rate caused by intravenous infusion of sodium nitroprusside (4 micrograms). These findings support a role for activation of neurons in the posterior nucleus of the hypothalamus in the generation of stress-induced cardiovascular changes and for control of this mechanism by local GABA receptors.

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