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Research has suggested that catalase plays a role in mediating ethanol's psychopharmacological effects. It has been shown that acatalasemic (C3H-A) mice differing in the activity of this enzyme consume larger amounts of ethanol. It has also been reported that when catalase activity is pharmacologically reduced, via 3-amino-1,2,4-triazole (AT), rats reduce their intake and preference for ethanol. The present research attempted to investigate AT's effects in nonselected mice. Swiss Webster mice were randomly assigned to groups of four per cage and further assigned to either a 5%, a 10%, or a 15% ethanol exposure condition. Mice were given a choice between water and increasing 1% concentrations of ethanol starting with 2%. Following five days of baseline, mice were injected daily with either AT (0.5 g/kg) or saline for five days. Results showed that AT significantly reduced ethanol consumption across treatment, but not posttreatment days. Results could not be explained by differences in total fluid intake. These results suggest a role for brain catalase in ethanol consumption across a variety of strains and species and further support the involvement of centrally formed acetaldehyde in the mediation of ethanol's psychopharmacological effects.

Chick embryos were given daily injections of ethanol (approximately 30 mg/day) either chronically from embryonic days 4 to 15 (E4-E15) or E18, or acutely from E15 to E18. Untreated and saline-injected embryos served as controls. Although morphological indicators of developmental age were not different among groups, chronic ethanol reduced weights of several brain regions. Similar to rodent models of prenatal ethanol exposure, chronic ethanol treatment reduced cerebellar Purkinje cell numbers compared to controls. Chronic but not acute ethanol exposure resulted in a significant reduction in choline acetyltransferase activity in the optic tectum (OT) and forebrain (FB) compared with controls. This study demonstrates that the chick embryo is a viable model to investigate the effects of ethanol exposure on CNS development. Unlike the mammalian fetus, the avian embryo is isolated from maternal interactions and may prove more useful in investigating the mechanisms by which ethanol directly influences brain development.

Although adolescent ethanol (EtOH) exposure has been associated with long-lasting changes in brain function, little is known as to whether EtOH exposure during adolescence alters sleep and cortical arousal. This study examined protracted alterations in sleep in adult rats exposed to EtOH during adolescence. Adolescent male Wistar rats were exposed to EtOH vapor for 12 h/day for 5 weeks. Cortical electroencephalograms were obtained during 4-h recording sessions after 5 weeks of withdrawal from EtOH. Adolescent EtOH exposure significantly reduced the mean duration of slow-wave sleep (SWS) episodes and the total amount of time spent in SWS in EtOH-exposed rats, compared to controls. Spectral analysis revealed that adolescent EtOH exposure significantly increased cortical peak frequencies during SWS in the 2-4, 4-6, and 6-8 Hz bands. Taken together, our findings suggest that chronic EtOH exposure in adolescent rats reduces measures of SWS, an effect also seen as part of normal aging. Although the cellular and molecular mechanisms mediating the consequences of EtOH exposure on the aging process are not known, the similarities between adolescent EtOH exposure and aging merits further investigation.

Two series of experiments were performed to determine the possible involvement of Ca++ channels in the thermolytic action of ethanol administered at a room temperature of 22 degrees C. In one group of 11 adult female Sprague-Dawley rats, stainless steel guide cannulae were implanted stereotaxically above the lateral cerebral ventricle. Prior to an experiment, a thermistor probe was inserted into the colon so that core temperature could be monitored continuously for up to six hours or until the temperature had returned to a previous baseline level. When the animal's body temperature had stabilized, a dose of 4.0 g/kg in a v/v solution of 20% ethanol was given by intragastric gavage. After the body temperature had declined by about 2.0 degrees C, ordinarily 30 min after ethanol administration, either control CSF or the vehicle plus one of four doses of verapamil (8.3, 25, 50 and 100 micrograms) was infused intracerebroventricularly (ICV) in a volume of 10 microliter. In a second group of 7 unoperated rats, either 4.0 g/kg ethanol or a physiological saline control solution was administered isovolumetrically by intragastric gavage; then, 30 min later, either 3.0 or 10.0 mg/kg verapamil was injected intraperitoneally. At an ambient temperature of 22 degrees C, ethanol gavage produced a significant decline in colonic temperature which was unaffected by physiological saline given by the same route. Although the CSF control vehicle was without effect, verapamil administered ICV attenuated the thermolytic action of ethanol in all doses tested; however, the lowest dose exerted its antagonist effect but with a longer latency. Conversely, when verapamil was given systemically, the hypothermic action of ethanol was significantly potentiated in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol (ETOH) administered acutely to castrate male rats caused a decline in pituitary luteinizing hormone (LH) and prolactin (PRL) secretion. This was associated with an elevation in hypothalamic and median eminence stores of dopamine (DA) that was related to the dose of alcohol given. Pituitary stalk transection (PST) resulted in a significant rise in plasma PRL levels compared to sham control animals, which suggests that DA in the hypophysial portal blood exerted an inhibitory influence on pituitary PRL secretion. The DA agonist bromocriptine failed to alter mean plasma LH levels in stalk-transected rats. The ETOH-treated castrated rats showed a significant rise in circulating PRL after injection of the DA receptor antagonist haloperidol metabolite II (HAL), but the administration of the DA receptor agonist R(-)-apomorphine HCL (APO) caused plasma PRL to decline to near undetectable levels. Plasma LH levels remained unchanged in the HAL- and APO-treated rats and were similar to those of sham controls. These results suggest that lactotroph DA receptors were still functional. Thus our previous finding of ETOH-induced reduction on LH secretion may be attributable to an inhibitory effect by DA on the luteinizing hormone-releasing hormone (LHRH) peptidergic neurons rather than a direct inhibition by DA on the pituitary gonadotroph.

Lead (Pb) is a developmental neurotoxicant that elicits differential responses to drugs of abuse. Particularly, ethanol consumption has been demonstrated to be increased as a consequence of environmental Pb exposure, with catalase (CAT) and brain acetaldehyde (ACD, the first metabolite of ethanol) playing a role. The present study sought to interfere with ethanol metabolism by inhibiting ALDH2 (mitochondrial aldehyde dehydrogenase) activity in both liver and brain from control and Pb-exposed rats as a strategy to accumulate ACD, a substance that plays a major role in the drug's reinforcing and/or aversive effects. To evaluate the impact on a 2-h chronic voluntary ethanol intake test, developmentally Pb-exposed and control rats were administered with cyanamide (CY, an ALDH inhibitor) either systemically or intracerebroventricularly (i.c.v.) on the last 4 sessions of the experiment. Furthermore, on the last session and after locomotor activity was assessed, all animals were sacrificed to obtain brain and liver samples for ALDH2 and CAT activity determination. Systemic CY administration reduced the elevated ethanol intake already reported in the Pb-exposed animals (but not in the controls) accompanied by liver (but not brain) ALDH2 inactivation. On the other hand, a 0.3 mg i.c.v. CY administration enhanced both ethanol intake and locomotor activity accompanied by brain ALDH2 inactivation in control animals, while an increase in ethanol consumption was also observed in the Pb-exposed group, although in the absence of brain ALDH2 blockade. No changes were observed in CAT activity as a consequence of CY administration. These results support the participation of liver and brain ACD in ethanol intake and locomotor activity, responses that are modulated by developmental Pb exposure.

Aldehyde dehydrogenase (ALDH) and catalase enzymatic activities in brain were assayed and compared to measures of alcohol consumption in two groups of animals screened and maintained on free-choice alcohol access under different conditions. In the first group of Long-Evans rats screened and maintained in home cages, mean alcohol intake was 3.49 g/kg/day with a range of 1.69-5.33 g/kg/day. When alcohol intake (g/kg), total ALDH, low K(m) ALDH, and catalase activities were entered in a multiple regression, a significant correlation of r = 0.51 (p < 0.05) was obtained. In the second group of rats consisting of Long-Evans, P, and NP rats screened using a drinkometer procedure, a multiple correlation between ALDH and catalase enzyme activities and alcohol intake of r = 0.42 (p < 0.05) was obtained. There was a strong relationship between the frequency of alcohol drinking bouts and the activities of catalase and ALDH (r = 0.68, p < 0.0001). The P rats had significantly higher catalase activities than either the NP or Long-Evans rats. The results of the present study confirmed earlier reports on the role of alcohol-metabolizing enzymes in the regulation of alcohol intake. The results also highlighted the fact that the activity of these alcohol-metabolizing enzymes may play a mediating role in patterns of alcohol intake displayed by animals selected for high and low alcohol drinking and also unselected animals.

The importance of the central catecholamines, with the emphasis on the noradrenergic neurons in the differential sensitivity to ethanol between the AT (alcohol-tolerant) rats selected for low and the ANT (alcohol-nontolerant) rats selected for high sensitivity to ethanol-induced (2 g/kg) motor impairment, was clarified by studying the effects of ethanol (2 and 4 g/kg, IP) on the utilization of norepinephrine (NA) and dopamine (DA), and on the metabolism of NA. The utilization of the catecholamines was estimated from the disappearance of the amines after inhibition of the brain tyrosine hydroxylase by alpha-methyl-p-tyrosine (200 mg/kg, IP), given 15 min after the administration of ethanol. The formation of 3-methoxy-4-hydroxy-phenylglycol (MHPG) was used as an estimate of NA metabolism, and was measured 30 min after the administration of ethanol. The basal utilization rate of NA and DA was similar between the two rat lines, but the increased formation of MHPG suggested that the naive AT rats had a higher noradrenergic activity in the limbic forebrain, hypothalamus, and cerebellum than did ANT rats. In the brain of both lines, ethanol accelerated the utilization and metabolism of NA in the same manner. Ethanol also increased the utilization of DA in the limbic forebrain of the AT and ANT rats. The higher sensitivity of the ANT rats' DA neurons to ethanol in the limbic forebrain and striatum was revealed by the significant rat line X ethanol interaction. The present findings suggest that the AT and ANT rats differ in the dopaminergic, but not in the noradrenergic responses to ethanol.