Diaz Silvina L, Kemmling Alma K, Balerio Graciela N
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 5 Piso, Argentina.
Neurochem Int. 2003 Mar;42(4):293-8. doi: 10.1016/s0197-0186(02)00102-x.
The present study analyzes the effects of baclofen (BAC) on mice brain neurochemical alterations during the morphine (MOR) withdrawal syndrome. Male Swiss-Webster albino mice (27-33 g) were rendered dependent by intraperitoneal (i.p.) injection of MOR (2mg/kg), twice daily for 9 days. On day 10, the dependent animals were divided into two groups: one receiving naloxone (NAL; 6 mg/kg i.p.) to precipitate the withdrawal syndrome 60 min after the last dose of MOR and the other received BAC (2mg/kg, i.p.) followed by NAL (6 mg/kg, i.p.), injected 30 and 60 min after the last dose of MOR, respectively. Ten minutes after these treatments, mice were killed by decapitation and the striatum, cortex and hippocampus were dissected to determine endogenous concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites using HPLC with electrochemical detection. Striatal DA, dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) concentrations as well as cortical DA concentrations of the withdrawal groups decreased significantly with respect to the control groups. BAC attenuated the decrease in DA and DOPAC concentrations observed during the withdrawal, without modifying per se the control DA concentrations. No changes on 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) concentrations were observed during the MOR abstinence syndrome. The prevention caused by BAC on the decreased concentrations of DA induced by MOR withdrawal could have a therapeutic interest for the management of withdrawal syndrome.
本研究分析了巴氯芬（BAC）对吗啡（MOR）戒断综合征期间小鼠脑内神经化学变化的影响。雄性瑞士-韦伯斯特白化小鼠（27-33克）通过腹腔注射MOR（2毫克/千克）使其产生依赖性，每天两次，共9天。在第10天，将依赖动物分为两组：一组接受纳洛酮（NAL；6毫克/千克腹腔注射），在最后一剂MOR后60分钟引发戒断综合征，另一组接受BAC（2毫克/千克，腹腔注射），随后分别在最后一剂MOR后30分钟和60分钟注射NAL（6毫克/千克，腹腔注射）。这些处理后10分钟，通过断头处死小鼠，解剖纹状体、皮质和海马，使用带电化学检测的高效液相色谱法测定多巴胺（DA）、5-羟色胺（5-HT）及其代谢物的内源性浓度。与对照组相比，戒断组的纹状体DA、二羟基苯乙酸（DOPAC）和高香草酸（HVA）浓度以及皮质DA浓度显著降低。BAC减轻了戒断期间观察到的DA和DOPAC浓度的下降，而本身并未改变对照DA浓度。在MOR戒断综合征期间，未观察到5-HT及其代谢物5-羟吲哚乙酸（5-HIAA）浓度的变化。BAC对MOR戒断引起的DA浓度降低的预防作用可能对戒断综合征的管理具有治疗意义。
