Cone Neurological Research laboratory, Department of Neurology and Neurosurgery, McGill University, 3801 University St., Montreal, QC, H3A2B4, Canada.
Psychopharmacology (Berl). 2009 Dec;207(2):315-23. doi: 10.1007/s00213-009-1659-4. Epub 2009 Sep 17.
Chronic treatment with the selective serotonin reuptake inhibitor, citalopram, normalizes several behavioral and neurochemical abnormalities in the olfactory bulbectomized (OBX) rat model of depression.
To assess the changes in regional cerebral glucose utilization (rCGU) following chronic treatment with citalopram in OBX and sham-operated rats.
Male Sprague Dawley rats (160-190 g) were used. Two weeks following the surgeries, the rats were implanted with osmotic minipumps which delivered 10 mg/kg/day of citalopram (the sham-CTP and OBX-CTP groups) or saline (to the sham-SAL and OBX-SAL groups) for 2 weeks. Following the treatment, the rates of rCGU were determined in 43 brain regions using 2-[(14)C]deoxyglucose (2-[(14)C]DG) autoradiography.
The general linear model statistical analysis revealed significantly lower rCGU in the OBX-SAL group compared to the sham-SAL group in the medial prefrontal cortex and the median forebrain bundle. The sham-CTP group had significantly lower rCGU relative to the sham-SAL group in the medial prefrontal cortex. The OBX-CTP group had significantly lower rCGU than the OBX-SAL group in the anterior olfactory nucleus, orbitofrontal cortex, frontal cortex, anterior cingulate cortex, visual cortex, and substantia nigra--pars reticulata. The rCGU in the OBX-CTP group was significantly lower than that in the sham-CTP group in the anterior olfactory nucleus, orbitofrontal cortex, visual cortex, and substantia nigra--pars reticulata.
The results imply that chronic citalopram treatment, shown previously to result in behavioral normalization in OBX rats, establishes a new pattern of rCGU, rather than normalizing it to the pattern of the sham-CTP rats.
慢性使用选择性 5-羟色胺再摄取抑制剂西酞普兰可使嗅球切除术(OBX)抑郁模型大鼠的多种行为和神经化学异常正常化。
评估慢性西酞普兰治疗对 OBX 和假手术大鼠局部脑葡萄糖利用率(rCGU)的影响。
使用雄性 Sprague Dawley 大鼠(160-190 g)。手术后 2 周,大鼠植入渗透微型泵,每天输送 10 mg/kg 的西酞普兰(假手术 CTP 和 OBX-CTP 组)或生理盐水(假手术 SAL 和 OBX-SAL 组)2 周。治疗结束后,使用 2-[14C]脱氧葡萄糖(2-[14C]DG)放射自显影技术测定 43 个脑区的 rCGU 率。
一般线性模型统计分析显示,与假手术 SAL 组相比,OBX-SAL 组内侧前额叶皮质和中脑束的 rCGU 显著降低。与假手术 SAL 组相比,假手术 CTP 组的内侧前额叶皮质 rCGU 显著降低。与 OBX-SAL 组相比,OBX-CTP 组在前嗅核、眶额皮质、额叶皮质、前扣带皮质、视皮质和黑质网状部的 rCGU 显著降低。与假手术 CTP 组相比,OBX-CTP 组在前嗅核、眶额皮质、视皮质和黑质网状部的 rCGU 显著降低。
这些结果表明,先前研究表明慢性西酞普兰治疗可使 OBX 大鼠的行为正常化,该治疗建立了新的 rCGU 模式,而不是使 rCGU 模式正常化至假手术 CTP 大鼠的模式。