OBJECTIVE: Post weanling isolation-reared (IR) rats are featured with depressive phenotype, yet its mechanism is not clearly defined particularly in terms of the involvement of central 5-HT1A receptors. The present study aims to examine the effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT depletion. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14 days after the surgery, rats were assessed their performance in FST with or without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY). RESULTS: 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC rats. IR rats were more immobile and less sensitive to the lesion-induced immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7-DHT lesion increased the expression of PFC 5-HT1A receptors. CONCLUSION: The integrity of central 5-HT system is developmentally crucial for the 5-HT1A-relevant depression profile in rats of social isolation.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Amygdala ; Animals ; Depression* ; Hippocampus ; Phenotype ; Prefrontal Cortex ; Rats* ; Receptor, Serotonin, 5-HT1A ; Serotonin 5-HT1 Receptor Agonists ; Serotonin* ; Social Control, Formal ; Social Isolation

OBJECTIVE: Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT. Seven days later rats entered a protocol of 8-OH-DPAT, a 5-HT1A agonist, in which locomotor activity, ASR and PPI and their tissue levels of 5-HT were measured. RESULTS: Our results found that both IR and 5,7-DHT decreased the tissue concentration of 5-HT. IR-induced hyperactivity and gating impairment were unaffected by 5-HT depletion. 8-OH-DPAT strengthened the ASR in IR but not SOC rats and the drug-reduced PPI could be adjusted by 5,7-DHT pretreatment. 8-OH-DPAT at 100 μg/kg enhanced PPI in 5-HT-depleted SOC rats. However for IR rats, 8-OH-DPAT strengthened PPI in sham rats but downgraded it in depletion condition. CONCLUSION: The integrity of central 5-HT system is important to 5-HT1A-modulated sensorimotor gating in isolation-reared rats.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Acoustics ; Animals ; Motor Activity ; Prepulse Inhibition ; Rats ; Receptor, Serotonin, 5-HT1A ; Reflex, Startle ; Sensory Gating ; Serotonin ; Serotonin 5-HT1 Receptor Agonists ; Social Control, Formal

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.