Pharmacology Biochemistry and Behavior最新文献

Post-traumatic stress disorder (PTSD) is increasingly recognized as a systemic disorder, with neuroendocrine, metabolic, and immune alterations accompanying its behavioral symptoms. While selective serotonin reuptake inhibitors such as fluoxetine are widely used to treat PTSD, their systemic effects during critical developmental periods remain poorly understood. Using a peripubertal rat model of PTSD-like stress, we evaluated the effects of fluoxetine administered during puberty on behavior (passive avoidance), serum biochemistry, hematology, and IL-6 levels. Assessments were conducted in two phases: shortly following the end of fluoxetine treatment and in a delayed post-treatment period. PTSD-like stress enhanced aversive memory retention, an effect attenuated by fluoxetine in the short post-treatment phase but not in the delayed period. Uric acid content in serum was increased in both PTSD and PTSD+fluoxetine groups shortly post-treatment, while LDL elevation was observed only in the delayed phase. The long-term effect of fluoxetine on serum creatinine was observed. Additional hematological alterations were observed in the delayed period. Serum IL-6 levels remained persistently elevated in PTSD group across both phases, indicating sustained inflammation with no clear effect of fluoxetine. Thus, peripubertal PTSD-like stress induces behavioral and metabolic alterations that persist beyond the acute stress period. Fluoxetine partially normalized behavior but failed to prevent long-term biochemical and hematological alterations. These highlight the systemic and time-dependent consequences of peripubertal PTSD and its pharmacological treatment, underscoring the need for longitudinal monitoring of physiological outcomes alongside recovery of behavioral phenotype.

Background: Pain-depression morbidity affects millions, but there are no effective treatments available. Dezocine is a clinically used opioid analgesic with complicated pharmacological mechanisms. Given this unique pharmacological profile and the crucial involvement of noradrenergic/serotonergic systems in the pathophysiology of depression, dezocine might be able to relieve pain-depression comorbidity. This possibility has not been tested and is the focus of this study. However, this potential has not yet been empirically validated, and investigating it constitutes the primary aim of this study.

Methods: Animal models of depression (Lipopolysaccharides [LPS] and chronic unpredictable mild stress models [CUMS]) were established, and two neuropathic pain models (chronic constriction injury [CCI] and spared nerve injury [SNI]) were used to establish chronic pain-induced depressive-like behaviors and the antidepressive-like effects of dezocine were then examined. Tail suspension test (TST) and force swimming test (FST) were used as behavioral readouts of antidepressant effects. For receptor mechanisms studies, 5-HT_1A receptor antagonist WAY-100635, nonselective opioid receptor antagonist naltrexone [NTX]), and three selective opioid receptor antagonists (μ: CTAP; δ: naltrindole [NAL]; k: nor-binaltorphimine [nor-BNI]) were used as pretreatment to antagonize the effects of dezocine.

Results: Dezocine (5 and 10 mg/kg, i.p.) significantly reduced immobility time, suggesting its robust antidepressive-like effects in stand-alone depression models and in neuropathic pain-induced depression models. WAY-100635, NTX, and CTAP but not NAL or nBNI blocked the antidepressive-like effects of dezocine, suggesting the involvement of 5-HT_1A and μ-opioid receptors in mediating the antidepressive-like effects of dezocine.

Conclusion: This study demonstrates that dezocine alleviates pain-depression comorbidity by activating both 5-HT_1A and μ-opioid receptor.