CB1 cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABAA receptor blockade in the dorsomedial division of the ventromedial hypothalamus

Anjos‐Garcia, Tayllon dos; Ullah, Farid; Falconi‐Sobrinho, Luiz Luciano; Coimbra, Norberto Cysne

doi:10.1016/j.neuropharm.2016.04.003

Cited by 39 publications

(22 citation statements)

References 53 publications

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“…84,93,94 Previous reports have shown that these nuclei are critically involved in the organization of innate defensive responses; this proposition is based on Fos immunoreactivity in rats exposed to natural predators, such as cats and snakes. 34,35,84,85,93 Other studies using electric or chemical stimulation of the hypothalamic defense system 62,63,[95][96][97][98] are in agreement with the findings using prey versus predator confrontations, and both these experimental models of panic attacks result in oriented escape reactions. 62,63,95,96 It is possible that the Fos-labeled neurons in the dorsal midbrain and the hypothalamic nuclei of rodents exposed to a live predator, to the odor of their skin, or to their excrements are indicative of the involvement of these structures in the elaboration of innate fear-induced behaviors, such as defensive alertness, defensive immobility and escape behavior.…”

Section: Neural Substrates Involved In Threatened Prey Animalssupporting

confidence: 67%

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

Coimbra

Paschoalin-Maurin

Bassi

et al. 2017

Rev. Bras. Psiquiatr.

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Section: Neural Substrates Involved In Threatened Prey Animalssupporting

confidence: 67%

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

Coimbra

Paschoalin-Maurin

Bassi

et al. 2017

Rev. Bras. Psiquiatr.

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“…In these responses, escape behavior, tachycardia, hypertension, and other dramatic manifestations of panic are followed by a depression/withdrawal state and antinociception (Freitas et al, 2013). Remarkably, this behavioral sequence can be triggered by disinhibiting neuronal clusters in the ventral DM or dorsomedial DM (VMHDM) with bicuculline (Freitas et al, 2013; Dos Anjos-Garcia et al, 2017). Furthermore, both the panic behavior and subsequent analgesia can be attenuated by a cannabinoid-1 (CB1) receptor antagonist administered in the VMHDM (Dos Anjos-Garcia et al, 2017) or prelimbic medial prefrontal cortex (Freitas et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Remarkably, this behavioral sequence can be triggered by disinhibiting neuronal clusters in the ventral DM or dorsomedial DM (VMHDM) with bicuculline (Freitas et al, 2013; Dos Anjos-Garcia et al, 2017). Furthermore, both the panic behavior and subsequent analgesia can be attenuated by a cannabinoid-1 (CB1) receptor antagonist administered in the VMHDM (Dos Anjos-Garcia et al, 2017) or prelimbic medial prefrontal cortex (Freitas et al, 2013). Both structures contain CB1 receptors (Wittmann et al, 2007; Tan et al, 2010; Reguero et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Cold-Induced Thermogenesis and Inflammation-Associated Cold-Seeking Behavior Are Represented by Different Dorsomedial Hypothalamic Sites: A Three-Dimensional Functional Topography Study in Conscious Rats

et al. 2017

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In the past, we showed that large electrolytic lesions of the dorsomedial hypothalamus (DMH) promoted hypothermia in cold-exposed restrained rats, but attenuated hypothermia in rats challenged with a high dose of bacterial lipopolysaccharide (LPS) in a thermogradient apparatus. The goal of this study was to identify the thermoeffector mechanisms and DMH representation of the two phenomena and thus to understand how the same lesion could produce two opposite effects on body temperature. We found that the permissive effect of large electrolytic DMH lesions on cold-induced hypothermia was due to suppressed thermogenesis. DMH-lesioned rats also could not develop fever autonomically: they did not increase thermogenesis in response to a low, pyrogenic dose of LPS (10 μg/kg, i.v.). In contrast, changes in thermogenesis were uninvolved in the attenuation of the hypothermic response to a high, shock-inducing dose of LPS (5000 μg/kg, i.v.); this attenuation was due to a blockade of cold-seeking behavior. To compile DMH maps for the autonomic cold defense and for the cold-seeking response to LPS, we studied rats with small thermal lesions in different parts of the DMH. Cold thermogenesis had the highest representation in the dorsal hypothalamic area. Cold seeking was represented by a site at the ventral border of the dorsomedial nucleus. Because LPS causes both fever and hypothermia, we originally thought that the DMH contained a single thermoregulatory site that worked as a fever–hypothermia switch. Instead, we have found two separate sites: one that drives thermogenesis and the other, previously unknown, that drives inflammation-associated cold seeking.SIGNIFICANCE STATEMENT Cold-seeking behavior is a life-saving response that occurs in severe systemic inflammation. We studied this behavior in rats with lesions in the dorsomedial hypothalamus (DMH) challenged with a shock-inducing dose of bacterial endotoxin. We built functional maps of the DMH and found the strongest representation of cold-seeking behavior at the ventral border of the dorsomedial nucleus. We also built maps for cold-induced thermogenesis in unanesthetized rats and found the dorsal hypothalamic area to be its main representation site. Our work identifies the neural substrate of cold-seeking behavior in systemic inflammation and expands the functional topography of the DMH, a structure that modulates autonomic, endocrine, and behavioral responses and is a potential therapeutic target in anxiety and panic disorders.

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“…The endocannabinoid system exerts multiple and complex modulatory physiological functions (Kendall and Yudowski, 2016; Ligresti et al, 2016; Argueta and DiPatrizio, 2017; Bennett et al, 2017; Dos Anjos-Garcia et al, 2017; Sun et al, 2017). For instance, cumulative evidence has suggested that the elements of the endocannabinoid system, including FAAH, control the sleep-wake cycle (Santucci et al, 1996; Murillo-Rodríguez et al, 1998, 2001, 2003, 2008a, 2011a, 2013, 2016; Herrera-Solis et al, 2010; Rueda-Orozco et al, 2010; Pava et al, 2014, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The endocannabinoid system is a complex biological arrangement that exerts multiple modulatory functions (Kendall and Yudowski, 2016; Ligresti et al, 2016; Argueta and DiPatrizio, 2017; Bennett et al, 2017; Dos Anjos-Garcia et al, 2017; Sun et al, 2017). The components of the endocannabinoid system include the most studied endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG; Di Marzo and Piscitelli, 2015; Yuan et al, 2016; Biernacki and Skrzydlewska, 2016; Correa et al, 2016; Huang et al, 2016; Lu and Mackie, 2016; Fakhoury, 2017).…”

Section: Introductionmentioning

confidence: 99%

Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

Murillo-Rodrı́guez

Marzo

Machado

et al. 2017

Front. Mol. Neurosci.

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The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB1 and CB2), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep–wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N-arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents.

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CB1 cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABAA receptor blockade in the dorsomedial division of the ventromedial hypothalamus

Cited by 39 publications

References 53 publications

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

Cold-Induced Thermogenesis and Inflammation-Associated Cold-Seeking Behavior Are Represented by Different Dorsomedial Hypothalamic Sites: A Three-Dimensional Functional Topography Study in Conscious Rats

Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

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