Maltose Dextrin Research Articles

Testing the spatial- versus object-learning distinction: water-maze performance of male rats exposed to ethanol during the brain growth spurt

This study investigated the effects of exposure to ethanol during the brain growth spurt on a visual-discrimination (VD) and a place-learning task (PL) using intra-maze cues in the water maze. Artificially reared male Long–Evans rats were exposed to ethanol (ET) in a binge pattern from postnatal days 6–9 (6.5 g · kg −1 · day −1; BAC ∼330 mg/dl) or an isocaloric maltose–dextrin solution (gastrostomy control). A third suckled control group was reared by lactating dams. In experiment 1, rats were trained to discriminate horizontal- (H) versus vertical-striped (V) cues, with the positive cue providing escape from water. Groups did not differ with V+, but ET rats made more errors with H+. In experiment 2, the ET group was impaired in learning the spatial location of a submerged platform relative to intra-maze cues. In both tasks, acquisition deficits among ET rats were characterized by impairment emerging at trial 2, with intact reference memory on trial 1, and the ET group reached a comparable level of performance to controls by the end of training. In summary, because impairment was related to task characteristics, a clear distinction between impaired spatial- versus cue-based learning was not supported. However, these findings do support an effect of exposure to ethanol during the brain growth spurt on recent event, but not reference, memory.

Exposure to ethanol and nicotine during the brain growth spurt: spatial DMP performance in male rats

Male Long–Evans rats were reared artificially and, using a 2×2 design, were exposed from postnatal days (PD) 6–9 to ethanol (ET: 6.5 g kg −1 day −1 “binge” exposure) and/or nicotine bitartrate (NIC: 6 mg kg −1 day −1 continuous exposure) via gastrostomy tubes. Controls were administered maltose–dextrin in amounts isocaloric to ET and/or sodium bitartrate. A fifth suckled-control group was reared normally. NIC accelerated eye opening on PD 14; whereas ET delayed eye opening and hindlimb support on PD 16. Beginning in postnatal week 7, rats were tested on a spatial delayed matching-to-place (DMP) version of the Morris water maze, which entailed a series of problems, each consisting of search and recall trials, that required the rats to use extra-maze cues to locate a hidden escape platform. In Phase 1 of testing, the ET-exposed groups were impaired in the recall trials, but there was no effect of NIC. A longer encoding time (45 vs. 10 s) improved performance across all groups. In contrast, acute administration of NIC (0.1 mg/kg ip) immediately prior to testing in Phase 2 failed to improve performance in any group. In conclusion, these results confirm previous findings of impaired spatial DMP-task performance in ET-exposed rats and further suggest that these memory deficits are amenable to amelioration.

Quantitative immunocytochemistry of glia in the cerebellar cortex of old ethanol-fed rats

It is clear from results of studies in this laboratory that chronic ethanol consumption causes regression of the extensive Purkinje neuron (PN) dendritic arbor. There are, however, a paucity of studies on the effects of chronic ethanol consumption on glia cells that reside in the molecular layer of the cerebellar cortex with PN dendrites. The purpose of the present study was to investigate the possibility that chronic ethanol consumption in old F344 rats results in gliosis within the molecular layer of the cerebellar cortex. Ten 12-month-old, male, F344 rats received a liquid diet containing 35% ethanol for 40 weeks. Pair-fed controls (n=10) received a liquid diet in which maltose dextrins were substituted for ethanol. Chow-fed rats (n=10) served as controls for age. At the end of the treatment period, rats were euthanized and perfused through the aorta, and cerebella were prepared for immunocytochemistry. Free floating sections were stained with (1) glial fibrillary acidic protein antibody for labeling of Bergmann glial cells and fibers, (2) OX-42 antibody for labeling of microglia, and (3) 0.5% cresyl violet for estimates of molecular layer volume. Results indicate that the densities of Bergmann glial cell processes and microglia within the cerebellar molecular layer are not altered by ethanol consumption.

Chronic Alcohol Consumption Attenuates Apoptosis by Down Regulation of P53 Expression in the Rat Pancreas.

INTRODUCTION. Heavy alcohol intake is a major cause of pancreatitis in humans, possibly through the regulation of apoptosis. Dysregulation of apoptosis has been considered a causative factor in several diseases. Emerging data show that ethanol intoxication interferes with the rate of apoptosis, which is deleterious to several organs, including the pancreas (1). We investigated a possible mechanism by which chronic alcohol feeding in rats may alter pancreatic homeostasis through a reduced apoptotic rate. METHODS. Rats were fed a liquid diet (Lieber-DeCarli) containing either ethanol or maltose dextrin in isocaloric amounts for 14 weeks. Pancreatic injury was assessed by plasma aamylase activity. Apoptosis was detected by in situ TUNEL assay, Caspase-3 and Caspase-8 activity. Messenger RNA expression of apoptotic factors and cytokines was investigated by RNase protection assay, while cpp32 (caspase-3), Fas ligand and PAP-1 mRNA expression was determined by semi-competitive RT-PCR. p53, Fas ligand, Bax and Bcl-2 protein expression was analyzed by western blotting. RESULTS. Chronic alcohol feeding significantly reduced serum a-amylase activity. p53 protein expression was dramatically diminished by alcohol administration. Caspase-3 mRNA and enzyme activity, caspase-8 activity, Bax mRNA and protein as well caspase-1 and -2 mRNA expression were also significantly reduced. Pancreatitis associated protein (PAP), a marker of pancreatic inflammation, showed a significantly reduced mRNA expression. We also found a non-significant trend toward decreases TUNEL positive nuclei in pancreata of alcohol fed rats. Chronic alcohol feeding suppressed the rate of apoptosis in the pancreas by diminishing the caspase activity and reducing the mRNA transcription level of intracellular pro-apoptotic factors. Alcohol did not affect the mRNA expression or the protein level of either anti-apoptotic factors or the Fas/FasL system.

Prenatal alcohol exposure decreases the number of nitric oxide synthase positive neurons in rat superior colliculus and periaqueductal gray

Because nitric oxide (NO) is involved in the development and refinement of axonal projections and synapses, it is of interest to know if developmental alcohol exposures affect NO producing neurons. Pregnant rats were fed artificial liquid diet throughout gestation as the only fluid or caloric source. The diet for experimental dams contained ethanol (6.7% v/v) while the pair-fed diet for control dams contained isocaloric maltose–dextrin instead of ethanol. This ethanol diet regime is known to produce peak blood alcohol concentrations of approximately 140 mg%. Cells stained histochemically for nitric oxide synthase (NOS) were counted at postnatal day 15 (P15) and 35 (P35) in cross-sections of the stratum griseum superficiale (SGS) of the superior colliculus (SC) and in the dorsolateral column of the periaqueductal gray (dlPAG). Compared to control tissues, alcohol caused the following effects: In the SC, the areal density of NOS+ neurons was decreased 24% at P15 but a similar decrease in means at P35 was not statistically significant ( P=0.10); soma size was unaffected at either P15 or P35. In the dlPAG, both the areal density and the total number of NOS+ neurons per section were unaffected at P15 but were decreased at P35 (33% and 37% decreases); soma size was unaffected at either P15 or P35. The decrease in NOS+ neurons in the SC at P15 could be expected to have a negative impact on the refinement of neuronal connections while the decreases in NOS+ neurons in the dlPAG at P35 likely represent more permanent effects that could alter the function of that nucleus.

Effect of quipazine, a selective 5-HT3agonist, on dietary self-selection of different macronutrient diets in male and female rats

Macronutrient intakes, 2h and 12h, following administration of a selective 5-HT3agonist, quipazine, N methyl, dimaleate (QUIPAZINE; 2·5, 5·0 and7·5mg/kg, i.p.) at dark onset were examined in three groups of adult male and female Wistar rats fed different sources of the three macronutrients: Group 1 (casein, corn starch, safflower oil), Group 2 (egg protein, corn starch/sucrose, lard) and Group S (casein hydrolysate, maltose dextrin, butter). QUIPAZINE decreased total food intake only in female rats from Group 1 (2h) at a dose of 7·5mg/kg and Group 2 (2h and 12h) with doses of 2·5 and 7·5mg/kg. Intakes from corn starch and corn starch/sucrose diet (12h) were reduced in male and female rats, respectively, with doses of 2·5 and 7·5mg/kg of QUIPAZINE. In conclusion, when provided with different sources of the three macronutrients, quipazine injection reduces specifically carbohydrate ingestion from corn starch-containing diets in male and female rats. Thus, the nature of the macronutrient source is of major importance to assess the effect of a drug on nutrient-specific selection.

Effect of Exogenous Thyroxine on the Development of the Purkinje Cell in Fetal Alcohol Effects in the Rat

The amelioration of fetal alcohol effects on the postnatal development of the Purkinje cell by exogenous L-thyroxine was investigated in the neonatal rat. Time-pregnant rats were divided into three groups. Group A (n = 6) received 35% liquid ethanol diet; Group B (n = 6) was fed a liquid diet in which maltose dextrins replaced alcohol isocalorically, constituting the pair-fed group; Group C (n = 6) received the 35% liquid ethanol diet and, in addition, received exogenous thyroxine (5 μg/kg/day) subcutaneously. After the pups were born, the mothers were removed and the pups of each were surrogate fostered by dams who were fed normal rat chow and water ad libitum. An average of six pups, one from each litter, were killed at days 7, 14, 21, and 28 for each of the above three groups. Light and electron microscopic observations of lobule II/III revealed a delayed alignment of Purkinje cells (Pc) in alcohol-exposed pups compared to pair-fed pups. The Pc of the pair-fed group showed a single-layer arrangement at 7 days which was seen only at day 14 in the alcohol group. However, in the alcohol + T4-exposed pups a single-layer arrangement was quite often seen at 7 days. Morphological observations showed impaired evidence of protein synthesis at all time sequences in the pups of Group A compared to Group B. A most interesting finding was the morphological evidence of greater protein synthesis in the Pc of the alcohol + T4 group at all times as indicated by a hypertrophied nucleus, abundant ribosomal collection, and numerous Nissl bodies.

Prenatal Binge-Like Alcohol Exposure in the Rat Results in Region-Specific Deficits in Brain Growth

Children of women who abuse alcohol during pregnancy may be affected by varying degrees of neurological abnormality, even if they are not diagnosed with Fetal Alcohol Syndrome. The extent of the behavioral deficits of the affected offspring may be a function of several factors, such as the differential vulnerability of the various regions of the brain-to-alcohol insult. In this study, groups of timed-pregnant rats were exposed to different doses of alcohol (EtOH 2.25, EtOH 4.5, EtOH 6.5 g/kg/day) or control conditions (maltose dextrin solution or no treatment) from embryonic day 1 (E1: sperm positive) to E20. On E33 (usually postnatal day 10), all pups were perfused. Their brains were removed, dissected into forebrain, cerebellum, and brainstem, and weighed. Blood alcohol concentrations (BACs) were measured on 4 different days of gestation, but the peak BACs across gestation for the three alcohol-treated groups averaged 142, 294, and 413 mg/dl for the EtOH 2.25, EtOH 4.5, and EtOH 6.5 g/kg groups, respectively. Analysis of the body weight data indicated that pups in the EtOH 6.5 g/kg group had a greater somatic growth deficit than pups from all other groups. Although the whole brain, forebrain, cerebellum, and brainstem weights of pups in the EtOH 6.5 g/kg group were significantly smaller than those in the control groups, within-treatment group analyses indicated that the cerebella of pups in the EtOH 6.5 g/kg group were more severely affected than were their forebrains or brainstems. The analyses of the brain region to body weight ratios revealed again that the cerebellum-to-body-weight ratio of pups in the EtOH 6.5 g/kg group was more severely affected than the forebrain or brainstem to body weight ratios. Collectively, these data lend support to the view that gross regions of the brain are differentially vulnerable to alcohol insult during the first two trimesters equivalent, and suggest that the cerebellum is vulnerable to injury from exposure to high BACs during a developmental period other than the third trimester equivalent.

Different central opioid receptor subtype antagonists modify maltose dextrin and deprivation-induced water intake in sham feeding and sham drinking rats

Different central opioid receptor subtypes participate in the mediation of intakes of simple (sucrose: μ, κ 1 and complex (maltose dextrin: μ) carbohydrates as well as deprivation-induced water intake (μ) under real-feeding and real-drinking conditions. An identical pattern of μ and κ 1 mediation of sucrose intake was observed in sham-feeding rats as well, suggesting their actions on orosensory mechanisms supporting sucose intake. The present study examined whether centrally administered general (naltrexone: 1–50 μg), μ (β-funaltrexamine: 1–20 μg), μ 1 (naloxonazine: 50 μg), κ 1 (nor-binaltorphamine: 1–20 μg), δ 1 ([ d-Ala 2, Leu 5, Cys 6]-enkephalin: 10–40 μg) or δ 22 (naltrindole isothiocyanate: 20 μg) opioid subtype antagonists altered either maltose dextrin (10%) intake during sham feeding or deprivation (24 h)-induced water intake during sham drinking in rats with gastric fistulas. Sham feeding significantly increased maltose dextrin intake (180%) and sham drinking significantly increased deprivation-induced water intake (256%) over a 60 min time course. Naltrexone significantly and dose-dependently reduced maltose dextrin intake (78%) in sham feeding rats, and deprivation-induced water intake (51%) in sham drinking rats. Maltose dextrin intake in sham feeding rats was significantly reduced by either κ 1 (69%) or δ 1 (59%) opioid antagonism, was significantly increased by μ 1 antagonism (43%), and was not significantly affected by either μ or δ 2 opioid antagonism. Deprivation-induced water intake in sham drinking rats was significantly reduced by either μ (41%), μ 1 (28%), δ 1 (48%) or δ 8 (28%) opioid antagonism, but was not significantly affected by κ 1 opioid antagonism. The difference in opioid receptor subtype mediation of maltose dextrin intake in real feeding and sham feeding conditions suggest that κ 1 and δ 1 receptors are involved in the orosensory mechanisms supporting maltose dextrin intake, while μ receptors are involved in the ingestive and post-ingestive mechanisms supporting maltose dextrin intake. The different patterns of opioid involvement in sucrose and maltose dextrin intake in sham feeding and real feeding conditions provide further support for the hypothesis that at least two different carbohydrate taste systems exist. The difference in opioid receptor subtype mediation of deprivation-induced water intake in real drinking and sham drinking conditions may reflect the removal in the sham drinking condition of a μ-mediated prerestorative satiety mechanism, and the unmasking of other opioid-mediated signalling mechanisms.

Chronic ethanol feeding in a high-fat diet decreases insulin-stimulated glucose transport in rat adipocytes.

Ethanol consumption has been associated with glucose intolerance and insulin resistance and is suggested to be an independent risk factor in the development of non-insulin-dependent diabetes mellitus. We have investigated the long-term effects of ethanol consumption on insulin-regulated glucose transport in rat adipocytes. Male Wistar rats were fed a high-fat liquid diet containing 35% ethanol (ethanol fed) or a control diet that isocalorically substituted maltose dextrin for ethanol (ad libitum). A third group was pair fed the control diet. Basal rates of 2-deoxyglucose uptake were similar in adipocytes from all three groups. Treatment with insulin increased 2-deoxyglucose uptake in ad libitum- and pair-fed rats but did not stimulate uptake in ethanol-fed rats. Similarly, although okadaic acid increased 2-deoxyglucose uptake in pair-fed rats, it had no effect in ethanol-fed rats. GLUT-1 quantity was greater in pair-fed and ethanol-fed rats compared with ad libitum controls. GLUT-4 was decreased in ethanol-fed compared with pair-fed rats but was not different from ad libitum controls. In ad libitum- and pair-fed rats, insulin increased the translocation of GLUT-4 to the cell surface by 2.0-fold. In contrast, translocation of GLUT-4 was not observed after insulin stimulation of ethanol-fed rats, paralleling the loss of insulin-stimulated glucose uptake. In ethanol-fed rats, GLUT-4 protein quantity was negatively associated with increased Gs alpha protein and isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate production. These data suggest that loss of insulin-stimulated glucose uptake in rat adipocytes after chronic ethanol feeding is at least partially due to decreased movement of GLUT-4 to the cell surface after insulin stimulation.

Ethanol consumption alters trafficking of lysosomal enzymes and affects the processing of procathepsin L in rat liver

In order to determine whether ethanol consumption alters the targeting of hepatic lysosomal enzymes to their organelles, we examined the sedimentation properties of lysosomal hydrolases in ethanol-fed rats and their pair-fed controls. Rats were fed a liquid diet containing either ethanol (36% of calories) or isocaloric maltose dextrin for one to five wk. Liver extracts were fractionated by Percoll density gradient centrifugation and fractions obtained were analyzed for the distribution of lysosomal marker enzymes. Heavy lysosomes were further purified from these gradients and the activity of specific hydrolases was determined. Compared with those from controls, isolated lysosomes from ethanol-fed rats showed a 20–50% reduction in the activity of lysosomal acid phosphatase and β-galactosidase. Decreased intralysosomal hydrolase activity in ethanol-fed rats was associated with a significant redistribution of these enzymes as well as those of cathepsins B and L to lighter fractions of Percoll density gradients. This indicated an ethanol-elicited shift of these enzymes to lower density cellular compartments. In order to determine whether ethanol administration affects the synthesis and proteolytic maturation of hepatic procathepsin L, we conducted immunoblot analyses to quantify the steady-state levels of precursor and mature forms of cathepsin L in hepatic post-nuclear fractions. Ethanol administration caused a significant elevation in the steady-state level of the 39 kDa cathepsin L precursor relative to its 30 kDa intermediate and 25 kDa mature product. These results were confirmed by pulse-chase experiments using isolated hepatocytes exposed to [ 35S]methionine. Hepatocytes from both control and ethanol-fed rats incorporated equal levels of radioactivity into procathepsin L. However, during the chase period, the ratios of the 39 kDa procathepsin L to its 30 kDa intermediate and 25 kDa mature product in cells from ethanol-fed rats were 1.5–3-fold higher than those in controls. These results demonstrate that ethanol consumption caused a marked impairment in the processing of procathepsin L to mature enzyme, without affecting its synthesis. Taken together, our findings suggest that chronic ethanol consumption caused a deficiency in intralysosomal enzyme content by altering the trafficking and processing of these hydrolases into lysosomes.

Equilibrative Adenosine Transport in Rat Hepatocytes after Chronic Ethanol Feeding

Acute treatment of cells with ethanol in vitro inhibits adenosine uptake via equilibrative nucleoside transporters. After longer periods of exposure to ethanol in culture, rechallenge with ethanol no longer inhibits adenosine uptake. Herein, we have investigated the long-term effects of ethanol consumption in vivo on equilibrative nucleoside transport. Rats were fed a liquid diet containing 35% of calories as ethanol (ethanol-fed). Control rats were pair-fed a liquid diet that isocalorically substituted maltose dextrins for ethanol. After 4 weeks of ethanol consumption, nucleoside transport was measured in isolated hepatocytes. Uptake of [3H]adenosine was lower in ethanol-fed rats compared with control. Influx of the nonmetabolizable nucleoside analog, [3H]formycin B, was also decreased after ethanol feeding. However, neither the number of nitrobenzylthioinosine (NBMPR) binding sites or inhibition of adenosine uptake by NBMPR were affected by ethanol feeding. In controls, acute treatment of isolated hepatocytes with 100 mM ethanol inhibited [3H]adenosine uptake by 30-40%. However, in ethanol-fed rats, acute challenge with ethanol did not inhibit [3H]adenosine uptake. These data demonstrate that long-term ethanol feeding decreases equilibrative nucleoside transport in hepatocytes independent of a change in the number of nucleoside transporters and renders adenosine uptake insensitive to inhibition by ethanol.

Nutritional value of protein hydrolysis products (oligopeptides and free amino acids) as a consequence of absorption and metabolism kinetics.

When pigs were submitted to duodenal infusion of solutions containing a large percentage of small peptides (PEP) or free amino acids with the same pattern (AAL) amino acids appear in the portal blood more rapidly and more uniformly after infusion of PEP then after infusion of AAL, with the notable exception of methionine for which the opposite was true. These differences were lowered when a carbohydrate (maltose dextrin) was present in the solution, but nevertheless remained significant for the first hour after the infusion. The long-term (8-hour) uptake of free amino acids into the liver and the peripheral tissues differed in profile according to the nature of the duodenal infusion. Peripheral uptake was appreciably less well balanced after infusion of free amino acids (deficiency of threonine and phenylalanine) than after infusion of small peptides (deficiency of methionine). Accordingly, in the rat, under conditions of discontinuous enteral nutrition the mixture of small peptides was of greater nutritive value than the mixture of free amino acids. It thus appears that the absorption kinetics which results in important variations in the temporal distribution of free amino acids in the tissues may be at the origin of transitory imbalances in tissue amino acid uptake, and as a result of a lower nutritive value.

Chronic ethanol feeding increases the quantity of Gα s-protein in rat liver plasma membranes

The liver is a primary target for both acute and chronic effects of ethanol. Because ethanol is known to alter the function of guanine nucleotide regulatory proteins (G-proteins), changes in hepatic G-proteins could contribute to the adverse effects of ethanol on liver function. Male Wistar rats were fed a liquid diet containing 36% of calories as ethanol for 4 weeks. Control rats were pair-fed or allowed free access to a diet that isocalorically substituted maltose dextrins for ethanol. Liver plasma membranes were isolated and separated into basolateral and canalicular fractions by sucrose-density gradients. Enrichment of marker enzymes (5′-nucleotidase for canalicular membranes and forskolin-stimulated adenylyl cyclase activity for basolateral membranes) was not affected by ethanol feeding. Quantity of Gα s and Gα i proteins in membrane fractions was determined by immunoblot. After ethanol feeding, immunoreactive Gα s protein was increased in liver plasma membranes compared with pair-fed controls. Gα i and Gα s were present in both the basolateral and canalicular fractions of the plasma membrane in control and ethanol-fed rats. Gα s quantity in the basolateral membrane was greater in ethanol-fed rats compared with controls, with no differences in Gα s observed in canalicular membranes. The quantity of Gα i did not change in response to ethanol feeding in any of the membrane fractions. Treatment of isolated plasma and basolateral membranes with 10 μmol/L 5′-guanylimidophosphate, a non-hydrolyzable guanosine triphosphate analogue that activates G-proteins, increased cAMP production to a greater extent in ethanol-fed rats compared with controls. These data indicate that ethanol increases the quantity and function of Gα s protein in rat liver plasma membranes.

Chronic ethanol feeding increases the quantity of Gαs-protein in rat liver plasma membranes

The liver is a primary target for both acute and chronic effects of ethanol. Because ethanol is known to alter the function of guanine nucleotide regulatory proteins (G-proteins), changes in hepatic G-proteins could contribute to the adverse effects of ethanol on liver function. Male Wistar rats were fed a liquid diet containing 36% of calories as ethanol for 4 weeks. Control rats were pair-fed or allowed free access to a diet that isocalorically substituted maltose dextrins for ethanol. Liver plasma membranes were isolated and separated into basolateral and canalicular fractions by sucrose-density gradients. Enrichment of marker enzymes (5'-nucleotidase for canalicular membranes and forskolin-stimulated adenylyl cyclase activity for basolateral membranes) was not affected by ethanol feeding. Quantity of G alpha s and G alpha i proteins in membrane fractions was determined by immunoblot. After ethanol feeding, immunoreactive G alpha s protein was increased in liver plasma membranes compared with pair-fed controls. G alpha i and G alpha s were present in both the basolateral and canalicular fractions of the plasma membrane in control and ethanol-fed rats. G alpha s quantity in the basolateral membrane was greater in ethanol-fed rats compared with controls, with no differences in G alpha s observed in canalicular membranes. The quantity of G alpha i did not change in response to ethanol feeding in any of the membrane fractions. Treatment of isolated plasma and basolateral membranes with 10 mumol/L 5'-guanylimidophosphate, a nonhydrolyzable guanosine triphosphate analogue that activates G-proteins, increased cAMP production to a greater extent in ethanol-fed rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Naltrexone, serotonin receptor subtype antagonists, and carbohydrate intake in rats

Functional interactions between serotonergic (5-HT) and opioid drugs have been observed with 5-HT 3 receptor antagonism enhancing the inhibitory actions of naloxone and naltrexone in both food-deprived and glucoprivic rats; 5- HT 2 A C receptor antagonism enhanced naltrexone's inhibition of insulin hyperphagia. The present study examined whether pretreatment with either general 5-HT (methysergide: 0.5–5 mg/kg), 5- HT 2 A C (ritanserin: 0.25–2.5 mg/kg), or 5-HT 3 (ICS 205930: 0.5–5 mg/kg) antagonists altered the pattern and magnitude of ad lib intake of simple (sucrose: 10%) or more complex (maltose dextrin: MD, 10%) carbohydrate solutions, or naltrexone's (0.25–2.5 mg/kg) inhibition of these forms of intake. Methysergide significantly increased the pattern and magnitude of sucrose intake at low (0.5–2.5 mg/kg) doses, and transiently delayed the pattern of MD intake at high (5 mg/kg) doses. Ritanserin significantly accelerated the pattern, but not the magnitude of sucrose intake at low (0.25–1.25 mg/kg) doses without affecting MD intake. ICS 205930 reduced the magnitude of sucrose intake at the highest (5 mg/kg) dose, and transiently reduced MD intake. Naltrexone dose dependently altered the pattern and magnitude of both sucrose and MD intake. Coadministration of ritanserin and naltrexone either eliminated or delayed the pattern of opioid antagonist inhibition of both sucrose and MD intake. Methysergide and ICS 205930 pretreatment produced minor changes in the pattern of naltrexone-induced inhibition. These data indicate that 5-HT receptor subtypes differentially modulate the pattern of carbohydrate intake, and indicate differential ingestive interactions between 5-HT and opioid antagonists under challenge and palatable conditions.

Differential effect of short-term ethanol on cardiac and vascular growth responses

To determine in rats the acute effect of ethanol on the activity of a marker of cardiac and vascular growth processes (ornithine decarboxylase) and on alpha 1-adrenergic-induced vascular trophic responses, and whether ethanol-induced sympathoadrenal hyperactivity stimulated vascular structural changes after a more prolonged treatment. Acute treatment was as follows: ethanol (5 g/kg, intubation), alpha 1-adrenergic agonist (10 mg/kg methoxamine subcutaneously), methoxamine plus ethanol, or control. Left ventricular, aortic and mesenteric vascular ornithine decarboxylase activity was determined 4 h later by measuring 14CO2 evolved from [14C]-ornithine. Three-day treatment was as follows: ethanol (every 8 h, intubation, 5 g/kg initial dose, subsequent doses based on intoxication level) or isocaloric quantities of maltose dextrin. The left ventricular: body weight ratio, hindlimb vascular resistance properties and indices of cardiac and vascular hypertrophy were determined. In the acute treatment methoxamine-induced pressor responses and the activation of vascular ornithine decarboxylase were both inhibited by ethanol treatment. Ethanol alone elevated the heart rate and decreased mean arterial pressure while stimulating left ventricular but not vascular ornithine decarboxylase activity. Methoxamine did not alter left ventricular ornithine decarboxylase activity. Three-day ethanol treatment induced cardiac hypertrophy but had no effect on the hindlimb vascular resistance properties measured at maximum dilation and maximum constriction. Acute and short-term ethanol exposure induces cardiac growth processes. Ethanol prevents alpha 1-adrenergic activated vascular growth response by a mechanism that may be similar to the attenuation of alpha 1-adrenergic-induced elevation of arterial pressure.

Central opioid receptor subtype antagonists differentially reduce intake of saccharin and maltose dextrin solutions in rats

Opioid modulation of ingestion includes general opioid antagonism of deprivation-induced water intake and intake of sucrose and saccharin solutions. Previous studies using selective subtype antagonists indicated that opioid effects upon deprivation-induced water intake occured through the mu 2 receptor and that opioid effects upon sucrose intake occured kappa and mu 2 receptors. The present study compared the effects of intracerebroventricular administration of opioid receptor subtype antagonists upon intakes of saccharin solution and a maltose dextrin (MD) solution to determine which receptor subtypes were involved in modulation of ingestion of different preferred tastants. Significant reductions in saccharin intake (1 h) occured following naltrexone (20–50 μg: 66%) and naltrindole (delta, 20 μg: 75%), whereas [ d-Ala 2, Leu 5, Cys 6]-enkephalin (DALCE, delta 1, 40 μg: 45%) had transient (5 min) effects. Neither beta-funaltrexamine (B-FNA, mu), naloxanazine (mu 1, nor nor-binaltorphamine (Nor-BNI, kappa) significantly altered saccharin intake. Significant reductions in MD intake (1 h) occured following naltrexone (5–50 μg: 69%) and B-FNA (1–20 μg: 38%). MD intake was not reduced by naltrindole, DALCE, naloxanazine and Nor-BNI. Peak antagonist effects were delayed (20–25 min) to reflect interference with the maintenance, rather than the initiation of saccharin or MD intake. Comparisons of opioid antagonist effects across intake situations revealed that naltrexone had consistently low ID 40 values for saccharin (29 nmol), MD (25 nmol), sucrose (6 nmol) and deprivation (38 nmol) intake. Despite its significant effects relative to naloxanazine, B-FNA had significantly higher ID 40 values for saccharin (800 nmol), MD (763 nmol) and sucrose (508 nmol) relative to deprivation (99 nmol) intake, suggesting that mu 2 receptors may be mediating maintenance of intake rather than taste effects. Nor-BNI had low 40 values intake of sucrose (4 nmol), but not for saccharin (168 nmol), MD (153 nmol) and deprivation (176 nmol), suggesting that kappa receptors may mediate ingestion of sweet-tasting stimuli. That delta (naltrindole: ID 40 = 60nmol), but not delta 1, (DALCE: ID 40 = 288nmol) antagonist consistently reduce saccharin intake suggests a role for the delta 2 receptor subtype in the modulation of hedonic orosensory signals.

Alcohol‐Induced Inhibition of Alveolar Macrophage Oxidant Release in Vivo and in Vitro

Alcohol consumption is known to predispose the host to more frequent and severe bacterial infections, suggesting that alcohol compromises the normal immune function of the lung. The pulmonary alveolar macrophage is the resident host defense cell in the lung and forms the first line of defense against invading microorganisms. One of the mechanisms whereby alveolar macrophages kill bacteria is by releasing toxic oxygen radical species, such as superoxide anion and hydrogen peroxide. We hypothesized that chronic alcohol consumption caused alveolar macrophage dysfunction leading to inhibition of oxidant production when stimulated. Our data demonstrate that alveolar macrophages harvested from alcohol-treated rats release significantly lower quantity (p < 0.05) of both superoxide anion and hydrogen peroxide when stimulated with several different types of stimuli including heat-killed Staphylococcus aureus, soluble immune complexes or phorbol myristate acetate. Pair-fed control rats who received isocaloric quantities of maltose dextrin in their diet to compensate for the alcohol were able to produce oxidants in equal quantities when stimulated, to rats who were fed a normal diet. Similar results were noted in vitro experiments when alveolar macrophages harvested from normal rats were incubated in vitro in alcohol-containing media and then stimulated with the aforementioned stimuli. Alveolar macrophages, which had been incubated in alcohol for 4 hr, showed significant decreases in their ability to produce superoxide anion. This defect was noticeable for a period up to 8 hr following removal of alveolar macrophages from the alcohol-containing media.(ABSTRACT TRUNCATED AT 250 WORDS)

Daily dose of ethanol and the development and decay of acute and chronic tolerance and physical dependence in rats

Using behavioral and physiological measures, we compared the rates of development and decay of acute and chronic tolerance to ethanol (ET) and the severity of the withdrawal syndrome. Male rats were treated with 6, 9, or 12 g/kg/day ET or equicaloric dextrin maltose, delivered intragastrically. Although treatment duration varied, the total dose of ET was kept constant at 162 g/kg/ rat for the three groups. The effects of a cumulative test dose of ET or equicaloric dextrin maltose, after exposure to a total of 0, 42, 83, 126, and 162 g/kg ET, and at 3, 5, and 7 days after termination of the chronic treatments, were evaluated on rectal temperature, dowel performance, and tail-flick and startle responses. After the initial five tolerance tests, chronic treatments were discontinued and rats were tested in a modified open-field apparatus and for their startle response to an auditory stimulus at 8, 12, 16, 20, 32, and 40 h later. With all measures, little tolerance developed in the 6-g/kg/day group. On the other hand, development of chronic tolerance was fastest in rats treated with the 12-g/kg/dose of ET. Chronic tolerance did not develop to ET's depressant effect on the startle response. Acute tolerance declined with chronicity of treatment in animals given the largest daily dose of ET. During withdrawal, and in contrast to the dextrin maltose-treated animals, there was impairment in all measures taken during the modified open-field test and hypersensitivity of the startle response for all three ET-treated animals. Greatest behavioral impairment occurred in animals treated with 12 g/kg/ day, and some impairment was still evident 40 h after the last dose of ET. Thus, the severity of the withdrawal syndrome was greatest in the group displaying the most acute and chronic tolerance.