Serotonin modulates social responses to stressed conspecifics via insular 5-HT 2C receptors in rat.

Autor: Ng AJ; Department of Psychology & Neuroscience, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA. Electronic address: ngaf@bc.edu., Vincelette LK; Department of Psychology & Neuroscience, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA., Li J; Department of Psychology & Neuroscience, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA., Brady BH; Department of Psychology & Neuroscience, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA., Christianson JP; Department of Psychology & Neuroscience, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2023 Sep 15; Vol. 236, pp. 109598. Date of Electronic Publication: 2023 May 23.
DOI: 10.1016/j.neuropharm.2023.109598
Abstrakt: Behaviors associated with distress can affect the anxiety-like states in observers and this social transfer of affect shapes social interactions among stressed individuals. We hypothesized that social reactions to stressed individuals engage the serotonergic dorsal raphe nucleus (DRN) which promotes anxiety-like behavior via postsynaptic action of serotonin at serotonin 2C (5-HT 2C ) receptors in the forebrain. First, we inhibited the DRN by administering an agonist (8-OH-DPAT, 1 μg in 0.5 μL) for the inhibitory 5-HT 1A autoreceptors which silences 5-HT neuronal activity. 8-OH-DPAT prevented the approach and avoidance, respectively, of stressed juvenile (PN30) or stressed adult (PN60) conspecifics in the social affective preference (SAP) test in rats. Similarly, systemic administration of a 5-HT 2C receptor antagonist (SB242084, 1 mg/kg, i.p.) prevented approach and avoidance of stressed juvenile or adult conspecifics, respectively. Seeking a locus of 5-HT 2C action, we considered the posterior insular cortex which is critical for social affective behaviors and rich with 5-HT 2C receptors. SB242084 administered directly into the insular cortex (5 μM in 0.5 μL bilaterally) interfered with the typical approach and avoidance behaviors observed in the SAP test. Finally, using fluorescent in situ hybridization, we found that 5-HT 2C receptor mRNA (htr2c) is primarily colocalized with mRNA associated with excitatory glutamatergic neurons (vglut1) in the posterior insula. Importantly, the results of these treatments were the same in male and female rats. These data suggest that interactions with stressed others require the serotonergic DRN and that serotonin modulates social affective decision-making via action at insular 5-HT 2C receptors.
Competing Interests: Declaration of competing interest The authors declare no direct or indirect biomedical financial interests or other potential conflicts of interest.
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Databáze: MEDLINE