Streeter Chris C, Hennen John, Ke Yong, Jensen J Eric, Sarid-Segal Ofra, Nassar Leanne E, Knapp Clifford, Meyer Angela A, Kwak Tae, Renshaw Perry F, Ciraulo Domenic A
Division of Psychiatry, Boston University School of Medicine, and Boston VA Healthcare System, Boston, MA, USA.
Psychopharmacology (Berl). 2005 Nov;182(4):516-26. doi: 10.1007/s00213-005-0121-5. Epub 2005 Oct 19.
There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA agonists decreases cocaine self-administration.
The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole, venlafaxine, or placebo.
CD subjects enrolled in a treatment trial for cocaine dependence were recruited for this proton (1H) magnetic resonance spectroscopy (MRS) study. GABA levels in the prefrontal lobe were measured before and after treatment.
Mean percentage changes in GABA levels were as follows: pramipexole +17.0+/-28.0%, venlafaxine +13.0+/-11.0%, and placebo -2.1+/-19.5%. Pramipexole-treated subjects had significantly increased brain GABA levels compared to placebo (p=0.031). Venlafaxine treatment was nonsignificantly associated with increased GABA levels compared to placebo (p=0.16). The overall statistical model for the effect of drug treatment vs placebo on brain GABA levels, including adjustment for baseline levels, was highly significant (p=0.002). Despite significant changes in GABA levels, there were no significant differences in the number of urine samples positive for cocaine metabolites.
This study demonstrates that 1H MRS can measure changes in GABA levels following pharmacologic treatment. The increase in GABA levels, although significant, is modest compared to other MRS studies of depression or epilepsy associated with clinical improvements. The failure to see larger increases in GABA levels and an associated reduction in cocaine consumption may reflect the relatively low doses of medication used.
有证据表明，可卡因依赖（CD）个体的前额叶γ-氨基丁酸（GABA）水平较低，且使用GABA激动剂治疗可减少可卡因的自我给药量。
本研究旨在测量CD受试者在基线时以及接受普拉克索、文拉法辛或安慰剂治疗8周后的GABA水平变化。
招募参加可卡因依赖治疗试验的CD受试者进行此项质子（1H）磁共振波谱（MRS）研究。在治疗前后测量前额叶的GABA水平。
GABA水平的平均百分比变化如下：普拉克索组为+17.0±28.0%，文拉法辛组为+13.0±11.0%，安慰剂组为-2.1±19.5%。与安慰剂组相比，普拉克索治疗组受试者的脑GABA水平显著升高（p=0.031）。与安慰剂组相比，文拉法辛治疗与GABA水平升高无显著相关性（p=0.16）。药物治疗与安慰剂对脑GABA水平影响的总体统计模型，包括对基线水平的调整，具有高度显著性（p=0.002）。尽管GABA水平发生了显著变化，但可卡因代谢物阳性的尿液样本数量并无显著差异。
本研究表明，1H MRS可测量药物治疗后GABA水平的变化。GABA水平的升高虽然显著，但与其他与临床改善相关的抑郁症或癫痫的MRS研究相比幅度较小。未能观察到GABA水平更大幅度的升高以及可卡因消耗量的相应减少，可能反映了所用药物剂量相对较低。
