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AbstractNon‐adaptive activation of dopamine transmission in the nucleus accumbens shell by drugs of abuse has been attributed a fundamental role in the mechanism of drug addiction. In order to test this hypothesis, we compared in the same subject the effect of an addictive drug (ethanol) and of taste stimuli, including ethanol's own taste, on dialysate dopamine in the nucleus accumbens shell as an estimate of dopamine transmission and on taste reactivity as an expression of motivational valence. Ethanol was also monitored in the dialysates. In naive rats, intraoral infusion of a 20% sucrose + chocolate solution elicited a monophasic increase of dialysate dopamine immediately after the intraoral infusion. In contrast, intraoral infusion of 10% ethanol, 10% ethanol + 20% sucrose or 10% ethanol + 20% sucrose + chocolate solutions elicited a biphasic increase of nucleus accumbens dopamine with an early taste‐related rise and a late rise related to dialysate ethanol. Pre‐exposure to the ethanol solutions 24 h before resulted in the absence of the early dopamine rise and permanence of the late dopamine rise. This late dopamine rise was actually increased as compared with that of the nonpre‐exposed group when sucrose‐containing ethanol solutions were tested. The results indicate that single trial pre‐exposure to the ethanol solutions differentially affects the responsiveness of nucleus accumbens shell dopamine to the direct intracerebral action of ethanol and to the effect of its taste with potentiation, or no change of the first and abolition of the second. These observations point to the existence of major differences in the adaptive regulation of nucleus accumbens dopamine transmission in the shell after drug as compared with taste reward. These differences, in turn, are consistent with a role of nucleus accumbens shell dopamine in the mechanism of the behavioural effects of addictive drugs.

Platelet aggregation, secretion of serotonin, and formation of thromboxane B2 induced by platelet-activating factor (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) were studied in plasma containing physiological concentrations of ionized calcium in eight alcoholics after cessation of heavy drinking. Responses of platelets of four nonalcoholic volunteers, matched with a subgroup of the alcoholics by age and sex, were also investigated. Aggregation of platelets from alcoholics was significantly less throughout the 6-day detoxification period compared with controls. Secretion of serotonin (5-hydroxy-tryptamine) was negligible and the production of thromboxane B2 was not detectable. Decreased platelet aggregability in response to aggregating agents, including platelet-activating factor, may be important in the development of hemorrhagic complications in alcoholics.

The effect of ethanol in vitro on inositol lipid metabolism in brain slices was investigated under nonstimulating and stimulating conditions. In cerebral cortical slices 100 microM norepinephrie (NE), 1 mM carbachol, 100 microM serotonin, 20 mM KCl, 1 mM glutamate and 30 microM A23187 stimulated inositide hydrolysis as measured by the release of [3H]inositol phosphates from [3H]myoinositol labeled slices. Ethanol (500 mM) inhibited nonstimulated inositide hydrolysis but had variable effects on stimulated inositide breakdown. NE-, KCl- and glutamate-stimulated [3H]inositol phosphate release was inhibited by 500 mM ethanol in the cortex. The inhibitory effect of ethanol on NE-stimulated inositide hydrolysis was concentration dependent and significant at concentrations as low as 100 mM. Inhibition by ethanol appeared to be noncompetitive. A similar pattern of inhibition by ethanol was observed when KCl was the stimulant. In hippocampal and hypothalamic slices, similar to cortical slices. NE- and KCl-stimulated inositide breakdown was significantly inhibited by ethanol. However, in brain stem slices, only KCl-stimulated [3H]inositol phosphate release was inhibited. Striatal slices stimulated by carbachol, NE and KCl were sensitive to the inhibitory effects of ethanol on inositol lipid breakdown. These results suggest that ethanol in vitro has specific effects on inositol lipid metabolism depending on the brain region studied and the type of stimulation. Moreover, the differential sensitivity to ethanol of stimulated inositide hydrolysis in the brain may contribute, at least in part, to some of the pharmacological effects of ethanol in vivo.

Background:  Ethanol (ETOH) consumption by pregnant women can result in Fetal Alcohol Spectrum Disorder (FASD). To date, the cellular targets and mechanisms responsible for FASD are not fully characterized. Our aim was to determine if ETOH can affect fetal human brain‐derived neural progenitor cells (NPC).Methods:  Neural progenitor cells were isolated by positive selection from normal second trimester fetal human brains (n = 4) and cultured, for up to 72 hours, in mitogenic media containing 0, 1, 10, or 100 mM ETOH. From 48 to 72 hours in culture, neurospheres generated in these conditions were filmed using time‐lapse video microscopy. At the end of 72 hours, neurosphere diameter and roundness were measured using videographic software. Mitotic phase analysis of cell‐cycle activity and apoptotic cell count were also performed at this time, by flow cytometry using propidium iodide (PI) staining. Real‐time PCR was used to estimate expression of genes associated with cell adhesion pathways.Results:  Neurosphere diameter correlated positively (r = 0.87) with increasing ETOH concentrations. There was no significant difference in cell‐cycle activity and no significant increase in apoptosis with increasing ETOH concentrations. Time‐lapse video microscopy showed that ETOH (100 mM) reduced the time for neurosphere coalescence. Real‐time PCR analysis showed that ETOH significantly altered the expression of genes involved in cell adhesion. There was an increase in the expression of α and β Laminins 1, β Integrins 3 and 5, Secreted phosphoprotein1 and Sarcoglycan ε. No change in the expression of β Actin was observed while the expression of β Integrin 2 was significantly suppressed.Conclusions:  ETOH had no effect on NPC apoptosis but, resulted in more rapid coalescence and increased volume of neurospheres. Additionally, the expression of genes associated with cell adhesion was significantly altered. ETOH induced changes in NPC surface adhesion interactions may underlie aspects of neurodevelopmental abnormalities in FASD.

Ethanol preference, a component of alcoholism, has been known for four decades to differ greatly between C57BL/6 and BALB/c inbred mouse strains. For mapping quantitative trait loci (QTLs) that affect ethanol preference, we used a set of B6.C Recombinant QTL Introgression (RQI) strains, which carry about 5% of the donor BALB/cJ (C) genome on a C57BL/6ByJ (B6) background. After characterizing males of the progenitor and RQI strains for variations in ethanol preference, we scanned their genome for polymorphisms at 244 dinucleotide-repeat marker loci known to differ between B6 and C. Because of the introgression of BALB/c-type QTLs onto the B6 background, some strains showed ethanol preference significantly lower or higher than that of the background strain, suggesting that genetic interaction between ethanol preference QTLs and the background can be operative. The genomic region showing the strongest influence on ethanol preference was on mouse chromosome 15, and corresponds to human chr.12q11-q13.

1. Several behavioral tests were used to compare two lines of mice selected for large (LB) and small brain (SB) weight on the basis of brain/body weight ratio values. 2. An elevated pain sensitivity as well more intense startle response was shown in SB mice in comparison with LB mice. 3. In inescapable situations of slip funnel and tail suspension tests, analogues of the Porsolt swim test, higher immobility scores in SB mice suggest an increased level of fear and/or anxiety the stress situations. 4. The SB mice demonstrated higher levels of locomotion in open field and cross-maze tests. In the latter test, the SB mice also showed increased tendency for stereotyped alternation of two arms during maze exploration. 5. Acute administration of a moderate dose of ethanol (3 g/kg) had opposite effects on the total time of cross-maze exploration: this measure increased in the SB and decreased in the LB line. By contrast, the tendency for stereotypy was similarly increased and the efficacy of maze exploration decreased in both lines.

Adenomyosis is characterized by the presence of ectopic endometrial tissue within the myometrium. Treatment options ranges from use of non-steroidal anti-inflammatory drugs and hormonal suppression for symptomatic relief, to endometrial ablation or even hysterectomy. In this paper we report the case of successful ultrasound-guided aspiration of focal adenomyosis with intracavitary alcohol instillation in a young patient with symptomatic juvenile cystic adenomyoma. This is the second report of the treatment of sclerotherapy by alcohol instillation, which may be considered as an alternative modality in treating the cases of symptomatic adenomyoma.

Ethanol intake and synaptosomal 3H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased in alcoholized Fawn-Hooded rats. These results indicate that synaptosomal 3H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholisation reduces 3H-serotonin internalisation in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system.

An investigation on the mechanism of neurochemical changes in physically or psychologically stressed mice was carried out. Physical stress was induced by electric foot shocks (2 mA for 5 s at 30-s intervals), and psychological stress was induced by emotional stimuli from electric foot-shocked mice using a communication box. The serum and brain calcium levels and immunohistochemical brain dopamine levels increased, and the ethanol-induced sleeping time was prolonged following exposure to these stimuli. The effects of electric foot shocks on these physiological parameters were greater than those of emotional stimuli. In the psychologically stressed mice, serum and brain calcium levels significantly increased 15 and 60 min, respectively, after the start of exposure to stimuli. Also, the immunohistochemical dopamine levels in the neostriatum and nucleus accumbens regions after 60 min of exposure to psychological stress were higher by 23% (P < 0.01) and 27% (P < 0.01), respectively, than those in unstressed control mice. Moreover, the ethanol-induced sleeping time was prolonged by approximately 60-100% (P < 0.01) in mice exposed to psychological stress for 30-120 min. The effect of emotional stimuli to prolong the ethanol-induced sleeping time was inhibited by intracerebroventricular administration of W-7 (a calmodulin antagonist) or alpha-methyltyrosine (an inhibitor of tyrosine hydroxylase). In light of previous reports that calcium activates dopamine synthesis in the brain via a calmodulin-dependent system, it is suggested that physical or psychological stimuli induce an increase in the brain calcium level, and this increased calcium level in turn enhances dopamine synthesis in the brain. Subsequently, an increased dopamine level induces various physiological changes related to stress-dependent phenomena.