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• W4328124228 abstract "ABSTRACT Background Aggressive behaviour (AB) may occur in patients with different neuropsychiatric disorders. Although most patients respond to conventional treatments, a small percentage continue to experience AB despite optimized pharmacological management and are considered to be treatment-refractory. For these patients, hypothalamic deep brain stimulation (pHyp-DBS) has been investigated. The hypothalamus is a key structure in the neurocircuitry of AB. An imbalance between serotonin (5-HT) and steroid hormones seems to exacerbate AB. Objectives To test whether pHyp-DBS reduces aggressive behavior in mice through mechanisms involving testosterone and 5-HT. Methods Male mice were housed with females for two weeks. These resident animals tend to become territorial and aggressive towards intruder mice placed in their cages. Residents had electrodes implanted in the pHyp. DBS was administered for 5h/day for 8 consecutive days prior to daily encounters with the intruder. After testing, blood and brain were recovered for measuring testosterone and 5-HT receptor density, respectively. In a second experiment, residents received WAY-100635 (5-HT 1A antagonist) or saline injections prior to pHyp-DBS. After the first 4 encounters, the injection allocation was crossed, and animals received the alternative treatment during the next 4 days. Results DBS-treated mice showed reduced AB that was correlated with testosterone levels and an increase in 5-HT1 A receptor density in the orbitofrontal cortex and amygdala. Pre-treatment with WAY-100635 blocked the anti-aggressive effect of pHyp-DBS. Conclusions This study shows that pHyp-DBS reduces AB in mice via changes in testosterone and 5-HT1 A mechanisms. HIGHLIGHTS - Posterior hypothalamus DBS reduces aggressive behavior in mice - Aggressive behavior was correlated with plasma testosterone levels - DBS increased 5-HT1A receptor density in the orbitofrontal cortex and amygdala - Pre-treatment with 5-HT1A antagonist (WAY) blocked the anti-aggressive effect of DBS" @default.
• W4328124228 created "2023-03-22" @default.
• W4328124228 creator A5006901906 @default.
• W4328124228 creator A5027108725 @default.
• W4328124228 creator A5058507775 @default.
• W4328124228 creator A5067783855 @default.
• W4328124228 creator A5089877909 @default.
• W4328124228 creator A5090699665 @default.
• W4328124228 date "2023-03-21" @default.
• W4328124228 modified "2023-09-27" @default.
• W4328124228 title "Reduction of aggressive behaviour following hypothalamic deep brain stimulation: involvement of 5-HT_1Aand testosterone" @default.
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