Injections of the α-2 adrenoceptor agonist clonidine into the dorsal raphe nucleus increases food intake in satiated rats

Flores, Rafael; Steinbach, Renata; Pedroso, João A.B.; Metzger, Martin; Donato, José; Paschoalini, Marta Aparecida

doi:10.1016/j.neuropharm.2020.108397

Cited by 3 publications

(5 citation statements)

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“…neurons of fed animals, leading to a decrease in 5-HT release in projection areas, which could favor ingestive behaviors (Flores et al, 2021). In fact, 5-HT release decreases after CLO injection into DR, and lesion with DSP-4 abolishes these effects (Bortolozzi and Artigas, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, in a previous study opposite feeding responses were induced by injection of α-adrenoceptors agonists into the DR of satiated rats. In the fed state, AD, NA, or CLO injection increased food intake while PHE treatment did not change feeding behavior ( Flores et al, 2021 ). Based on these findings, the hyperphagic effect was attributed to the inhibition of NA release in DR noradrenergic terminals by the activation of α-2 presynaptic auto-receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Based on these findings, the hyperphagic effect was attributed to the inhibition of NA release in DR noradrenergic terminals by the activation of α-2 presynaptic auto-receptors. This activation removes a possible endogenous α-1 adrenergic stimulatory tone on DR serotonergic neurons of fed animals, leading to a decrease in 5-HT release in projection areas, which could favor ingestive behaviors ( Flores et al, 2021 ). In fact, 5-HT release decreases after CLO injection into DR, and lesion with DSP-4 abolishes these effects ( Bortolozzi and Artigas, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies demonstrated that 5-HT acts as a satiety signal in hypothalamic nuclei, such as the arcuate and the paraventricular nuclei, as well as other areas such as the parabrachial nucleus and nucleus of the solitary tract ( Voigt and Fink, 2015 ). Stimulation of DR neurons increases extracellular 5-HT levels in the hypothalamus ( De Fanti et al, 2000 ) and manipulation of adrenoceptor activity in the DR induces FOS expression in discrete populations of arcuate and paraventricular nucleus neurons ( Flores et al, 2021 ). Thus, it is possible that activation of DR α-1 adrenoceptors by PHE results in 5-HT release in fasted animals, since facilitatory control of 5-HT release is attributed to these receptors ( Bortolozzi and Artigas, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, we demonstrated that injection of α-2 agonist clonidine into the DR of satiated rats evoked hyperphagia ( Flores et al, 2021 ). The feeding response induced by clonidine was similar to that found after noradrenaline or adrenaline injections into the DR, suggesting that this hyperphagia depends on α-2 adrenoceptors activation, while injection of a specific α-1 agonist did not affect food intake ( Flores et al, 2021 ). Based on these previous data, we hypothesized that injection of α-adrenoceptor agonists into DR may also affect ingestive responses in fasted animals.…”

Section: Introductionmentioning

confidence: 99%

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α-1 Adrenoceptor Activation in the Dorsal Raphe Nucleus Decreases Food Intake in Fasted Rats

et al. 2021

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The dorsal raphe (DR) nucleus is involved in a myriad of physiological functions, such as the control of sleep-wake cycle, motivation, pain, energy balance, and food intake. We have previously demonstrated that in ad libitum fed rats the intra-DR administration of phenylephrine, an α-1 receptor agonist, does not affect food intake, whereas clonidine, an α-2 receptor agonist, potently stimulates food intake. These results indicated that in fed rats an increased adrenergic tonus blocked food intake, since the activation of α-2 auto-receptors, which decreases pre-synaptic release of adrenaline/noradrenaline, affected food intake. Thus, in this study we assessed whether the response to adrenergic stimuli would differ after overnight fasting, a situation of low adrenergic activity in the DR. Intra-DR administration of adrenaline and noradrenaline blocked food intake evoked by overnight fasting. Similarly, phenylephrine administration decreased hunger-induced food intake. These changes in food intake were accompanied by changes in other behaviors, such as increased immobility time and feeding duration. On the other hand, intra-DR administration of clonidine did not affect food-intake or associated behaviors. These results further support the hypothesis that in fed animals, increased adrenergic tonus in DR neurons inhibiting feeding, while in fasted rats the adrenergic tonus decreases and favors food intake. These data indicate a possible mechanism through which adrenergic input to the DRN contributes to neurobiology of feeding.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%