Janiri L, Gobbi G, Persico A M, Santarelli M, Minciacchi D, Tempesta E
Department of Psychiatry, Faculty of Medicine, Catholic University, Rome, Italy.
Alcohol Alcohol. 1994 Sep;29(5):611-9.
Alcohol is known to be a CNS teratogenic factor interfering with neuronal and synaptic maturation. The purpose of this microiontophoretic study was to explore GABAergic and cholinergic central mechanisms in adult rats exposed to alcohol in the third phase of prenatal life (ADM), when their mothers were subjected to alcohol physical dependence induction (9.6 g/kg/day). Responses to acetylcholine and GABA were recorded in frontal and somatosensory cortical neurons. Adult rats, whose mothers had been administered placebo with identical procedures, were used as a control (C). Cholinergic responses were significantly decreased and GABAergic responses increased in ADM animals with respect to controls. After a single i.p. alcohol injection (1.6 g/kg) spontaneous firing was depressed in ADM animals to a lesser extent than in C rats. Cholinergic excitations were reduced in C group and potentiated with reversal of atropine antagonism in ADM animals. GABAergic inhibitions were slightly increased and bicuculline antagonism was blocked in C rats, while ADM animals showed decreased responses to GABA. The present results support the hyperactivity of GABAergic system and the hypoactivity of cholinergic system reported in previous studies on prenatally and postnatally alcohol-exposed animals. Microiontophoretic results following ethanol injection led to the hypothesis that a rapid tolerance/dependence may develop in the offspring of alcohol-dependent rats.
已知酒精是一种中枢神经系统致畸因素,会干扰神经元和突触的成熟。本微离子电泳研究的目的是探讨成年大鼠在产前生活第三阶段暴露于酒精(ADM)时的GABA能和胆碱能中枢机制,此时它们的母亲接受酒精身体依赖诱导(9.6克/千克/天)。记录额叶和体感皮层神经元对乙酰胆碱和GABA的反应。将母亲以相同程序给予安慰剂的成年大鼠用作对照(C)。与对照组相比,ADM动物的胆碱能反应显著降低,GABA能反应增加。单次腹腔注射酒精(1.6克/千克)后,ADM动物的自发放电受到的抑制程度小于C组大鼠。C组的胆碱能兴奋降低,而ADM动物中阿托品拮抗作用的逆转使其增强。C组大鼠的GABA能抑制略有增加,荷包牡丹碱拮抗作用被阻断,而ADM动物对GABA的反应降低。目前的结果支持先前关于产前和产后暴露于酒精的动物研究中报道的GABA能系统亢进和胆碱能系统功能减退。乙醇注射后的微离子电泳结果导致这样一种假设,即酒精依赖大鼠的后代可能会迅速产生耐受性/依赖性。