Sucrose consumption increases naloxone-induced c-Fos immunoreactivity in limbic forebrain

Opioids have long been known to have an important role in feeding behavior, particularly related to the rewarding aspects of food. Considerable behavioral evidence suggests that sucrose consumption induces endogenous opioid release, affecting feeding behavior as well as other opioid-mediated behaviors, such as analgesia, dependence, and withdrawal. In the present study, rats were given access to a 10% sucrose solution or water for 3 wk, then they were injected with 10 mg/kg naloxone or saline. Brains were subsequently analyzed for c-Fos immunoreactivity (c-Fos-IR) in limbic and autonomic regions in the forebrain and hindbrain. Main effects of sucrose consumption or naloxone injection were seen in several areas, but a significant interaction was seen only in the central nucleus of the amygdala and in the lateral division of the periaqueductal gray. In the central nucleus of the amygdala, naloxone administration to those rats drinking water significantly increased c-Fos-IR, an effect that was significantly enhanced by sucrose consumption, suggesting an upregulation of endogenous opioid tone in this area. The data from this study indicate that the central nucleus of the amygdala has a key role in the integration of gustatory, hedonic, and autonomic signals as they relate to sucrose consumption, if not to food intake regulation in general. Furthermore, the data from this study lend further support to the hypothesis that sucrose consumption induces the release of endogenous opioids.     

Mescaline-induced changes of brain-cortex ribosomes. Role of spermidine in counteracting the destabilizing effect of mescaline on brain-cortex ribosomes

1. The effect of spermidine on the mescaline-induced changes of brain-cortex ribosomes was studied by adding spermidine during the treatment of goat brain-cortex slices with mescaline. 2. Mescaline treatment of brain-cortex slices removed a portion of the endogenous spermidine from ribosomes and this removal was significantly prevented when spermidine was present during mescaline treatment. 3. Spermidine present during mescaline treatment of brain-cortex slices counteracted, to some extent, the destabilizing effect of mescaline on ribosomes with respect to heat denaturation. 4. Mescaline treatment of brain-cortex slices made ribosomes more susceptible to breakdown, releasing protein and RNA, and resulting in loss of ribosomal enzymic activities. However, spermidine present during mescaline treatment counteracted moderately the mescaline-induced ribosomal susceptibility to breakdown and ribosomal loss of enzymic activities. 5. Ribosomes of mescaline-treated cortex slices were rapidly degraded by ribonuclease and trypsin. However, if spermidine was present during mescaline treatment of brain-cortex slices the rates of degradation diminished.     

High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation

High-fructose corn syrup-55 (HFCS-55) has been suggested to be more lipogenic than sucrose, which increases the risk for nonalcoholic fatty liver disease (NAFLD) and dyslipidemia. The study objectives were to determine the effects of drinking different sugar-sweetened solutions on hepatic gene expression in relation to liver fatty acid composition and risk of NAFLD. Female rats were randomly assigned (n=7 rats/group) to drink water or water sweetened with 13% (w/v) HFCS-55, sucrose or fructose for 8 weeks. Rats drinking HFCS-55 solution had the highest (P=.03) hepatic total lipid and triglyceride content and histological evidence of fat infiltration. Rats drinking HFCS-55 solution had the highest hepatic de novo lipogenesis indicated by the up-regulation of stearoyl-CoA desaturase-1 and the highest (P<.001) oleic acid (18:1n-9) content. This was accompanied by reduced β-oxidation indicated by down-regulation of hepatic peroxisome proliferator–activated receptor α. Disposal of excess lipids by export of triglyceride-rich lipoprotein from the liver was increased as shown by up-regulation of gene expression of microsomal triglyceride transfer protein in rats drinking sucrose, but not HFCS-55 solution. The observed lipogenic effects were attributed to the slightly higher fructose content of HFCS-55 solution in the absence of differences in macronutrient and total caloric intake between rats drinking HFCS-55 and sucrose solution. Results from gene expression and fatty acid composition analysis showed that, in a hypercaloric state, some types of sugars are more detrimental to the liver. Based on these preclinical study results, excess consumption of caloric sweetened beverage, particularly HFCS-sweetened beverages, should be limited.     

Radioimmunoassays of 3,4,5-trimethoxyphenethylamine (mescaline) and 2,5-dimethoxy-4-methylphenyl-isopropylamine(DOM)

Mescaline (3,4,5-trimethoxyphenethylamine) and N-succinylmescaline were coupled to human serum albumin with carbodiimide. DOM (2,5-dimethoxy-4-methylphenylisopropylamine) was linked to human serum albumin by reaction with glutaraldehyde. These conjugates were used for immunization of rabbits. Derivatives of mescaline [N-(3′,4′,5′-trimethoxyphenethyl)-4-hydroxyphenylacetamide] and of DOM [N-(2′,5′-dimethoxy-4′-methylphenylisopropyl)-4-hydroxyphenylacetamide], which could be iodinated to high specific activity, were synthesized. The antibodies bound specifically to these iodinated compounds. In competition experiments with a mescaline antiserum, 6 pmoles of mescaline inhibited 50%; with a DOM antiserum, 50% inhibition was observed with 118 pmoles of DOM. Thus, 100 pg of mescaline and 2 ng of DOM can be detected. The specificity of both antibodies is such that structurally related molecules, such as p-methoxy-phenethylamine or 3-methoxytyramine, are several orders of magnitude less effective as inhibitors than the parent molecules. With the use of antimescaline, it was determined that mescaline administered intravenously to rabbits disappeared rapidly from the circulation. The acid was identified as the major metabolite in the serum and urine of these animals.     

Effect of mescaline on an innate behaviour of mice

The action of mescaline on mice innate behaviour was studied. In the first experiment the drug modified the innate behaviour of mice. The dose-effect curve was obtained by the second. The results pointed out that, in the range of doses examined, there was one for which the disruptive action of mescaline reach the maximum so that mice behaviour became completely casual.     

A moment-by-moment comparsion of sucrose and saccharin drinking by the rat

Comparisons were made between the ingestion patterns in ratsto a 0.2% sodium saccharin solution and to a 32% sucrose solutionin both short-term (30 min, one solution only) and long-term(23 h, solution versus water) tests. The resolution of measurementin the short- and long-term tests was 0.5 and 30 s respectively.Analysis programs for both procedures allowed for a quantificationof the ingestion patterns over time, showing details of thelick bursts in the short-term tests and ingestion bouts in the23-h tests. Although the quantities of sucrose and saccharinconsumed in the long-term tests were equal, the drinking patternsfor water, saccharin and sucrose were markedly different duringthe three testing periods, (i) There were fewer drinking boutsto the sucrose than to the saccharin or water, (ii) The averagebout of sucrose was much larger than the saccharin or waterbouts, (iii) The inter-bout intervals for sucrose were muchlonger than those for saccharin, (iv) Nearly half of the sucroseintake occurred during the ‘lights-on’ portion ofthe 23-h drinking period as compared to less than one-thirdfor saccharin or water, (v) Food intake when saccharin was presentwas equal to normal food intake when only water was available.However, in the presence of sucrose, the number and the sizeof feeding bouts decreased resulting in a 36% reduction in foodintake. Similar results were found in the short-term tests whencomparing sucrose and saccharin ingestion in that the quantitiesconsumed were not reliably different, but the ingestion patternswere, (i) The rats had many more bursts of licking saccharinthan sucrose, (ii) The saccharin bursts were much shorter thanthose for sucrose, (iii) Saccharin licking occurred off andon throughout the 30-min testing period while sucrose was consumedat a rapid rate at first and then terminated in 10–15min from the period onset. Inferences about the different tastesof saccharin and sucrose to the rat arc drawn from the detailedpattern analyses.     

Simultaneous observation of ingestive and copulatory behavior of the male rat.

In a preliminary test male rats were allowed to ingest a 1 M solution of sucrose from a drinking spout. After daily intake of sucrose became stabilized, the males were given a sexually receptive or non-receptive female and the bottle filled with sucrose solution simultaneously. The ingestive and copulatory behavior was observed for 60 min under illumination by a red lamp. The data obtained from this study showed that the ingestive behavior of males was suppressed by the presence of sexually receptive females and, conversely, the sexual behavior of males was not affected by the presence of a bottle of sucrose. These results suggest that the presence of a sexual partner inhibits appetitive ingestive behavior, i.e., the responses used by male rats to obtain food.     

Chronic binge-like moderate ethanol drinking in rats results in widespread decreases in brain serotonin, dopamine, and norepinephrine turnover rates reversed by ethanol intake

This research was initiated to assess the turnover rates (TORs) of dopamine (DA), norepinephrine (NA), serotonin (5-HT), aspartate, glutamate, and GABA in brain regions during rodent ethanol/sucrose (EtOH) and sucrose (SUC) drinking and in animals with a history of EtOH or SUC drinking to further characterize the neuronal systems that underlie compulsive consumption. Groups of five male rats were used, with two trained to drink EtOH solutions, two to drink SUC and one to serve as a non-drinking control. When stable drinking patterns were obtained, rats were pulse labeled intravenously and killed 60 or 90 min later and the TORs of DA, norepinephrine, 5-HT, aspartate, glutamate, and GABA determined in brain regions. Changes in the TOR of 5-HT, DA, and NA were detected specific to EtOH drinking, SUC drinking or a history of EtOH or SUC drinking. An acute EtOH deprivation effect was detected that was mostly reversed with EtOH drinking. These results suggest that binge-like drinking of moderate amounts of EtOH produces a deficit in neuronal function that could set the stage for the alleviation of anhedonic stimuli with further EtOH intake that strengthen EtOH seeking behaviors which may contribute to increased EtOH use in at risk individuals.     

Estimation of mescaline and pellotine in Lophophora coulter plants (Cactaceae) by means of the oscillographic polarography

Oscillographic polarography has been applied for the mescaline and pellotine estimation. These alkaloids produce in 0.5 N NaOH electrolyte a sharp peak within the cathode region of the oscillogram, each of them showing different potential. It makes possible to estimate them at a concentration of 5.10(-6) g/ml. All the forms of Lophophora williamsii were found to contain mescaline and lower content of pellothine, L. jourdaniana--to have equal content of both alkaloide, L. diffusa and L. fricii--to contain pellotine and only traces of mescaline. Plants grown in the greenhouse accumulated the same amount of alkaloids as native plants. Grafting on roodstock which does not produce essential amount of the alkaloids, does not affect the ability of Lophophora to synthesize mescaline and pellotine.     

Effects of mescaline and its derivative N-[3,4,5-trimethoxyphenylethyl]-aziridine on the spatial orientation of rats in a T-maze

The central effect of mescaline and of its derivative N-[3,4,5- trimethoxyphenylethyl]-aziridine (FAZ) after their stereotaxic administration into the lateral ventricle of the brain was studied in behavioural experiments on rats. The effect of the two substances was tested by a method studying memory elicitation in response to appetitive motivation in a multiple T-maze. The results show that both substances worsened the behaviour in question. The negative effect of mescaline (lengthening of the time of passage through the maze) was manifested both immediately and several weeks after a single dose. FAZ likewise worsened the test reaction, but its effect was less pronounced than that of mescaline.     

The effect of mescaline, 3, 4-dimethoxyphenethylamine and 2, 5-dimethoxy-4-methylamphetamine on rat plasma prolactin: evidence for serotonergic mediation.

Mescaline, 3,4-dimethoxyphenethylamine (DMPEA) or 2,5-dimethoxy-4-methylamphetamine (DOM) was administered to male Sprague-Dawley rats, alone or in combination with para-chlorophenylalanine (PCPA), an inhibitor of serotonin (5-HT) synthesis, or methysergide, a 5-HT receptor blocker. All three compounds increased plasma prolactin (PRL) levels. These increases were potentiated by PCPA and blocked by methysergide. Pretreatment with alpha-methylparatyrosine (AMPT), an inhibitor of catecholamine synthesis, resulted in an increase in plasma PRL equal to the additive effects of the independent administration of mescaline, DMPEA, or DOM plus the AMPT-induced response. The results suggest that mescaline, DMPEA and DOM may be exerting their effects on rat plasma PRL through direct stimulation of serotonin receptors. These results further demonstrate the ability of PCPA to rapidly induce supersensitivity of the 5-HT receptors which stimulate PRL secretion.     

Tamoxifen produces conditioned taste avoidance in male rats: An analysis of microstructural licking patterns and taste reactivity

Estrogen receptor activation has been shown to reduce body weight and produce a conditioned reduction in food intake in male rats that is putatively mediated by estradiol's suggested aversive effects. Evidence has shown that the selective estrogen receptor modulator tamoxifen used in the prevention and treatment of breast cancer may also produce changes in food intake and body weight, which are known to impact cancer development and survival. The purpose of the present study was to examine whether tamoxifen produces a conditioned reduction in intake similar to estradiol by producing a conditioned aversion. A one bottle lickometer test was used to examine conditioned changes in sucrose drinking, while the taste reactivity test was used to measure rejection reactions, which serve to index aversion in rats. A backward conditioning procedure that consisted of 3 conditioning days and one vehicle test day was used to examine conditioned changes in 0.3 M sucrose intake and taste reactivity. Our results show that tamoxifen produced a conditioned reduction in sucrose drinking in a one bottle fluid intake test that was similar to the effects produced by estradiol (positive control); however, no active rejection reactions were produced by either tamoxifen (1 and 10 mg/kg) or estradiol. The present results suggest that tamoxifen, at the doses used in the present study, acts as an estrogen receptor agonist to regulate food intake and that the conditioned reduction in intake produced by tamoxifen and estradiol reflects conditioned taste avoidance rather than conditioned taste aversion.     

Tet-On Induction with Doxycycline after Gene Transfer in Mice: Sweetening of Drinking Water is not a Good Idea

Gene transfer to skeletal muscle leads to long-term, stable expression of transferred genes. An exiting development is the use of inducible expression systems. Using the inducible Tet-On system, it has been customary to administer doxycycline in drinking water with added sucrose to ameliorate the bitter taste. During a study aiming at regulating electrotransferred genes through the Tet-On system, we observed excessive drinking behavior among mice. Removal of sugar from the drinking water led to normal drinking behavior and most importantly did not affect the level of gene expression. Based on this study, the practice of adding sucrose to drinking water in doxycycline induction studies should be abandoned.     

Tet-On induction with doxycycline after gene transfer in mice: sweetening of drinking water is not a good idea

Gene transfer to skeletal muscle leads to long-term, stable expression of transferred genes. An exiting development is the use of inducible expression systems. Using the inducible Tet-On system, it has been customary to administer doxycycline in drinking water with added sucrose to ameliorate the bitter taste. During a study aiming at regulating electrotransferred genes through the Tet-On system, we observed excessive drinking behavior among mice. Removal of sugar from the drinking water led to normal drinking behavior and most importantly did not affect the level of gene expression. Based on this study, the practice of adding sucrose to drinking water in doxycycline induction studies should be abandoned.     

Regional localization of [14C]mescaline in rabbit brain after intraventricular administration

Albino rabbits of either sex were anesthetized, and a cannula was implanted permanently into the lateral ventricle. About 1 week later, the distribution of [¹⁴C]mescaline and its deaminated metabolite, [¹⁴C]trimethoxyphenylacetic acid ([¹⁴C]TMPA) in 12 brain regions was examined at 15, 60, and 180 min after the intraventricular injection of [¹⁴C]mescaline (0.5 mol in 0.05 ml saline).¹⁴C-radioactivity was rapidly distributed in all regions, reaching peak levels within 15 min. The spinal cord, superior colliculus, pons, hypothalamus, caudate, medulla oblongata, and inferior colliculus contained 23–57 nmol/g of mescaline; the thalamus, tegmentum, and cerebellum, 12–15 nmol/g; and the cerebrum and hippocampus, less than 10 nmol/g; the levels of [¹⁴C]TMPA ranged from 0.5 to 5 nmol/g. The levels of [¹⁴C]mescaline and of [¹⁴]TMPA in all brain areas were considerably decreased 180 min after its injection. Pretreatment with chlorpromazine (15 mg/kg, i.p., 30 min) lowered [¹⁴C]mescaline concentrations in the hippocampus, caudate, thalamus, and cerebrum and elevated them in the spinal cord, medulla oblongata, pons, and tegmentum; [¹⁴C]TMPA levels as the percentage of total radioactivity were not affected. Pretreatment with iproniazid (150 mg/kg, i.p., 18 h), on the other hand, uniformly reduced the TMPA levels in all brain areas, with the resultant increases in mescaline levels. The CPZ-effect in lowering the mescaline concentrations in the areas belonging to the limbic system may have significance in explaining its antihallucinogenic effect in humans and its ability to block the altered behavior induced by the latter drug in laboratory animals.     

Phenylthiocarbamide produces conditioned taste aversions in mice

Previous work has demonstrated that SWR/J (SW) mice avoid phenylthiocarbamide (PTC) to a greater degree than C3HeB/FeJ mice in 48 h, two-bottle preference tests given in ascending series. The authors hypothesized, based also on previous work, that SW mice might form a conditioned taste aversion over time due to the toxic properties of PTC. We directly tested this hypothesis by attempting to condition a taste aversion to sucrose by injections of PTC. In experiment 1, PTC was nearly as effective as a strong dose of LiCl in reducing sucrose drinking. In experiment 2, the sucrose aversions were parametrically modified by both sucrose concentration and PTC dose, a hallmark of conditioned taste aversion. We conclude that PTC can cause a conditioned taste aversion and discuss the importance of considering toxic effects of aversive tastants when analyzing behavioral strain differences.     

Hallucinogens as a discriminative stimuli: generalization of DOM to a 5-methoxy-N, N-dimethyltryptamine stimulus.

Hallucinogens (psychotomimetic agents) are capable of producing various discriminative stimuli for animals. Serotonergic involvement has been implicated as playing a role in the behavioral effects elicited by, for example, mescaline and DOM. Because certain tryptamine analogs possess high serotonin (5-HT) receptor binding affinities, it was of interest to examine one of the more potent agents. Employing a standard operant test chamber, six rats were trained to respond under a variable-interval 15-second schedule of sweetened-milk reinforcement. 5-Methoxy-N, N-dimethyltryptamine (5-OMe DMT), which possesses a 5-HT receptor affinity much higher than that of mescaline, but nearly equivalent to that of DOM, was found to serve as a discriminative stimulus. Furthermore, the 5-OMe DMT stimulus could be attenuated by the 5-HT antagonist BC-105. The 5-OMe DMT stimulus generalized with DOM suggesting that these two hallucinogens produce qualitatively similar interoceptive cues in rats.     

Effect of mescaline on cerebral cholinesterases and on exploratory behavior in rats]

In this study the Authors had the purpose to evaluate the action of a psychotomimetic substance (mescaline) on behavior (exploring behaviour and spontaneous motility) and on cerebral biochemistry (cholinesterase activity) of rat. The mescaline has shown to be active both on behaviour (increasing the spontaneous motility) and on biochemistry (decreasing the total cholinesterase activity). From the examination of the results of this work it could be cautiously assumed the hypothesis that the behavioural effects of mescaline are related (at least partially) to modifications of the cholinergic system at the cerebral level.     

Cardiovascular responses to water drinking: does osmolality play a role?

Water drinking activates the autonomic nervous system and induces acute hemodynamic changes. The actual stimulus for these effects is undetermined but might be related to either gastric distension or to osmotic factors. In the present study, we tested whether the cardiovascular responses to water drinking are related to water's relative hypoosmolality. Therefore, we compared the cardiovascular effects of a water drink (7.5 ml/kg body wt) with an identical volume of a physiological (0.9%) saline solution in nine healthy subjects (6 male, 3 female, aged 26 +/- 2 years), while continuously monitoring beat-to-beat blood pressure (finger plethysmography), cardiac intervals (electrocardiography), and cardiac output (thoracic impedance). Total peripheral resistance was calculated as mean blood pressure/cardiac output. Cardiac interval variability (high-frequency power) was assessed by spectral analysis as an index of cardiac vagal tone. Baroreceptor sensitivity was evaluated using the sequence technique. Drinking water, but not saline, decreased heart rate (P = 0.01) and increased total peripheral resistance (P < 0.01), high-frequency cardiac interval variability (P = 0.03), and baroreceptor sensitivity (P = 0.01). Neither water nor saline substantially increased blood pressure. These responses suggest that water drinking simultaneously increases sympathetic vasoconstrictor activity and cardiac vagal tone. That these effects were absent after drinking physiological saline indicate that the cardiovascular responses to water drinking are influenced by its hypoosmotic properties.