• Energy Research

Ethanol may act at the enkephalinergic receptor level through condensation products such as salsolinol. This fact has been demonstrated by studying the 'in vitro' and 'in vivo' salsolinol interaction on enkephalinergic receptor sites labeled by [3H-Met] enkephalin. The modification induced by chronic ethanol and salsolinol on this neuronal system is a reduction of the affinity of the receptor for its ligand. These data suggest that a down regulation process due to the continuous opiate receptor stimulation occurs after ethanol administration.

Prolonged ethanol treatment modifies various neurotransmitter systems. GABAergic neuronal function was particularly affected. On the other hand, clinical reports have indicated an interaction between ethyl alcohol and benzodiazepine receptors. These observations suggest a possible site of action of ethanol at the level of the GABA-benzodiazepine receptor complex. Our results showed that ethanol treatment differentially affected GABA receptor function and benzodiazepine binding sites. When [3H]GABA binding in the cerebellum, striatum and hippocampus was increased, [3H]diazepam binding remained unchanged in the same areas. The possibility of modulation of ethanol effects on GABAergic neurons through benzodiazepine receptors is discussed.

The fetal alcohol syndrome is characterized by a number of abnormalities consisting of a pre- and post-natal growth deficiency, microcephaly, areas of abnormal nerve cell migration in the brain, mental and psychomotor retardation in children of alcoholic women. These findings may be referred as a teratogenic effect of ethanol on the central nervous system. In order to investigate the above ethanol-neurotoxic effect the striatal dopaminergic transmission was studied. The dopaminergic turnover was measured by 3,4-dihyroxyphenilacetic acid content and 3H-Spiperone binding has been carried out to determine dopaminergic receptor alterations induced by chronic ethanol consumption during pregnancy. Our work demonstrates long-lasting modifications of dopaminergic neuronal function after exposure of the experimental animal to ethanol during fetal life. In particular, a decreased receptor function has been observed in rats exposed to ethanol only during the perinatal period. In the same group of rats, diminished receptor activity leads to an enhancement in DOPAC content still detectable after a long period from cessation of ethanol treatment. Neurochemical data are reinforced by behavioral observations. In fact, a significant decrease of spontaneous locomotor activity in the rats chronically treated with ethanol during fetal life was observed. In addition, the altered response of locomotor activity after drug administration may be ascribed to the modified dopaminergic function. With this experimental approach we assume that the action of ethanol on the central nervous system may be a marker of its teratogenic effect.

Chronic ethanol consumption induces an increase in striatal adenylate cyclase enzymatic activity but is unable to further potentiate the dopamine stimulated production of cyclic-AMP. In striatal membranes obtained from chronic ethanol-treated rats, apomorphine exerts a more potent inhibition of [3H]spiperone binding when compared with controls, demonstrating that ethanol increases the affinity of the dopaminergic receptors associated with adenylate cyclase activity. In addition, GTP is unable to modify the agonist component of dopamine receptor in membrane exposed 'in vivo' to ethanol. Data are discussed in terms of a derangement of receptor-adenylate cyclase coupling system produced by chronic ethanol treatment.