Ethanol-conditioned flavor preferences compared with sugar- and fat-conditioned preferences in rats

Rats can learn to prefer flavors paired with ethanol and various nutrients. The present study examined the relative strengths of flavor preferences conditioned by 5% ethanol and isocaloric solutions of 7.18% sucrose, 7.18% fructose, or 3.26% corn oil. In three experiments, nondeprived rats were trained with different flavored solutions (conditioned stimuli, CS) paired with intragastric (IG) infusions: a CS+E flavor paired with ethanol infusion, a second CS+ paired with a nutrient infusion, and a CS- paired with water infusion. In two-bottle tests, rats strongly preferred a sucrose-paired CS+S over the CS- and over the CS+E. The preference for the CS+E over CS- was weaker. These effects occurred when the rats drank substantially more CS+S than CS+E in training and when training intakes were matched. Similar results were obtained when the nutrient infusion was fructose or corn oil, except that preferences for the CS+F or CS+O over the CS+E were less pronounced than with CS+S. Consistent with the IG results, rats trained to drink flavored sucrose and ethanol solutions preferred the CS+S to CS+E in a flavored water test. These results confirm prior reports of ethanol-conditioned preferences but show that ethanol is less effective than other nutrients at isocaloric concentrations. The marked individual differences in ethanol-conditioned preferences may be related to the impact of the sugar or fat infusions on the reward evaluation of the ethanol-paired flavor.     

Differential effects of removing the glucose or saccharin components of a glucose-saccharin mixture in a successive negative contrast paradigm

When rats experience an unexpected decrease in reward value, e.g., from 32% sucrose to 4% sucrose, consummatory behavior abruptly decreases to a level below control subjects that only experience the lesser reward, a phenomenon known as Successive Negative Contrast (SNC). In food deprived rats experiencing downshifts in sucrose concentration, SNC dissipates in 3-4 days, as consummatory behavior in shifted rats recovers to the level of unshifted controls. In Experiment 1 food deprived rats that were given 5 min daily access to a 2% glucose-0.15% saccharin mixture, and subsequently shifted to 2% glucose alone, displayed a dramatic SNC effect relative to rats that only received 2% glucose. This SNC effect was primarily manifested as a decrease in the number of consummatory bursts initiated. Interestingly, intake failed to recover to control levels during eight daily postshift sessions. However, in Experiment 2 subjects that were shifted from the same glucose-saccharin mixture to 0.15% saccharin alone failed to show SNC rather, intake fell to the level of control animals which only received 0.15% saccharin. The data from Experiment 1, in conjunction with previous studies utilizing non-deprived rats, quinine adulteration, or shifts from sucrose to saccharin, show that reductions in taste value can produce contrast effects, but suggest that a threshold caloric value is necessary for recovery. The data from Experiment 2 may suggest that saccharin and glucose do not contribute equally to the enhanced palatability of the mixture.     

Backward conditioning of tumor necrosis factor-α in a single trial: changing intervals between exposures to lipopolysaccharide and saccharin taste

The current study examined the effect of backward conditioning with three different time intervals between exposures to lipopolysaccharide (LPS) as the unconditioned stimulus (US) and saccharin taste in water as the potential conditioned stimulus (CS). Forty-eight naïve female BALB/c mice at three months of age served as subjects, divided into six groups. Four groups were assigned to Experiment 1 for the tumor necrosis factor alpha (TNF-α) measure, and the remaining two groups were used in Experiment 2 to measure taste aversion behavior. Both experiments employed a single trial. The timing of introduction to the saccharin taste varied between 3 min, 7 h, and 24 h following an LPS injection in Experiment 1. Experiment 2 employed the three-minute interval only. These intervals correspond to distinct immunological, physiological, and behavioral events induced by LPS. On the day after re-exposure to the saccharin taste, the TNF-α groups were challenged with LPS to test the LPS tolerance response. While backward conditioning of taste aversion behavior was not observed, some evidence of conditioned TNF-α response and subsequent development of LPS tolerance was observed with backward conditioning in a single trial. This exploratory study demonstrated that the effect of backward conditioning on conditioned TNF-α response and LPS tolerance response in a single trial depended on the timing of when a CS is presented after LPS exposure.     

Melanin-concentrating hormone receptor 1 (MCH1-R) antagonism: reduced appetite for calories and suppression of addictive-like behaviors

Rationale

The hypothalamic neuropeptide melanin-concentrating hormone and its MCH1 receptor have been implicated in regulation of feeding and energy homeostasis, as well as modulation of reward-related behaviors. Here, we examined whether the MCH system plays a role both in caloric and motivational aspects of sugar intake.

Materials and methods

The non-peptide MCH1-R antagonist GW803430 (3, 10, 30 mg/kg, i.p.) was first tested on self-administration under a fixed ratio schedule of reinforcement of both a caloric (10% w/v sucrose) and a non-caloric (0.06% w/v saccharin) sweet solution. GW803430 was then tested for its ability to alter motivational properties and seeking of sucrose. Lastly, the drug was tested to concurrently examine its effects on the escalated consumption of both sugar and food in animals following intermittent sugar access.

Results

The MCH1-R antagonist reduced sucrose- but not saccharin-reinforced lever pressing, likely reflecting a decreased appetite for calories in GW803430-treated rats. GW803430 reduced sucrose self-administration under a progressive ratio schedule, and suppressed cue-induced reinstatement of sucrose seeking, suggesting effects on rewarding properties of sucrose. GW803430 attenuated food intake in rats on intermittent access to sucrose at all doses examined (3, 10, 30 mg/kg), while reduction of sugar intake was weaker in magnitude.

Conclusion

Together, these observations support an involvement of the MCH system in regulation of energy balance as well as mediation of sucrose reward. MCH may be an important regulator of sugar intake by acting on both caloric and rewarding components.     

Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia

Although many artificial sweeteners (AS) have safety issues, the AS have been widely used in industry. To determine the physiologic effect of AS in the presence of hyperlipidemia, zebrafish were fed aspartame or saccharin with a high-cholesterol diet (HCD). After 12 days, 30% of zebrafish, which consumed aspartame and HCD, died with exhibiting swimming defects. The aspartame group had 65% survivability, while the control and saccharin groups had 100% survivability. Under HCD, the saccharin-fed groups had the highest increase in the serum cholesterol level (599 mg/dL). Aspartame-fed group showed a remarkable increase in serum glucose (up to 125 mg/dL), which was 58% greater than the increase in the HCD alone group. The saccharin and HCD groups had the highest cholesteryl ester transfer protein (CETP) activity (52% CE-transfer), while the HCD alone group had 42% CE-transfer. Histologic analysis revealed that the aspartame and HCD groups showed more infiltration of inflammatory cells in the brain and liver sections.Conclusively, under presence of hyperlipidemia, aspartame-fed zebrafish exhibited acute swimming defects with an increase in brain inflammation. Saccharin-fed zebrafish had an increased atherogenic serum lipid profile with elevation of CETP activity.     

Electrochemical and thermal studies of the ternary complex of Cu(II) with saccharin and nicotinamide

The electrochemical behaviour and thermal decomposition of a ternary complex of Cu(II) with saccharin and nicotinamide have been investigated by means of voltammetric (square-wave and cyclic voltammetry), spectroscopic and thermoanalysis (TG, DTA, DTG) measurements. The electrochemical data show that the ternary complex undergoes reduction at a more negative potential (?0.310 V) when compared to the binary complexes; Cu(II)–nicotinamide (a shoulder at ?0.164 V) and Cu(II)–saccharinate (?0.252 V). ESR spectra (room temperature) of the complex showed a broad signal (g_⊥=2.064) due to the weak anti-ferromagnetic coupling between the Cu atoms. ESR and magnetic susceptibility data suggest that the structure of the complex is square–pyramidal in the solid state. The thermal behaviour of the complex from ambient temperature up to 1000 °C in a static air atmosphere was studied. The decomposition pathway of the complex is interpreted in terms of the structural data. A possible mechanism for the decomposition of the complex is proposed.     

Total avoidance of saccharin consumption by rats after repeatedly paired injections of ethanol or LiCl

Rats injected with ethanol or LiCl following consumption of novel saccharin solution drank less saccharin than non-poisoned controls on a subsequent exposure with degree of aversion positively related to dose of ethanol (2–5 g/kg). While a single pairing of saccharin with ethanol or LiCl resulted in partial avoidance of saccharin,solution, repeated conditioning trials led to total avoidance of saccharin consumption by animals injected with the higher doses of ethanol or with LiCl. These results, characteristic of emetic-induced aversions, support the explanation of the limited consumption of ethanol by rats under ad lib, free-choice conditions as a result of acquired aversion to the oronasal sensory stimuli of ethanol after association with pharmacologically aversive aftereffects of consumed ethanol.     

Voluntary ethanol consumption in 22 inbred mouse strains

Inbred strains are genetically stable across time and laboratories, allowing scientists to accumulate a record of phenotypes, including physiological characteristics and behaviors. To date, the C57/C58 family of inbred mouse strains has been identified as having the highest innate ethanol consumption, but some lineages have rarely or never been surveyed. Thus, the purpose of the present experiment was to measure ethanol preference and intake in 22 inbred mouse strains, some of which have never been tested for ethanol consumption. Male and female mice (A/J, BALB/cByJ, BTBR + T^tf/tf, BUB/BnJ, C57BL/6J, C57BLKS/J, C58/J, CZECH/Ei, DBA/2J, FVB/NJ, I/LnJ, LP/J, MA/MyJ, NOD/LtJ, NON/LtJ, NZB/B1NJ, NZW/LacJ, PERA/Ei, RIIIS/J, SEA/GnJ, SM/J, and 129S1/SvlmJ) were individually housed and given unlimited access in a two-bottle choice procedure to one bottle containing tap water and a second containing increasing concentrations of ethanol (3%, 6%, 10%), 0.2% saccharin, and then increasing concentrations of ethanol (3%, 6%, 10%) plus 0.2% saccharin. Mice were given access to each novel solution for a total of 4 days, with a bottle side change every other day. Consistent with previous studies, C57BL/6J (B6) mice consumed an ethanol dose of >10 g/kg/day whereas DBA/2J (D2) mice consumed <2 g/kg/day. No strain voluntarily consumed greater doses of ethanol than B6 mice. Although the C58 and C57BLKS strains showed high ethanol consumption levels that were comparable to B6 mice, the BUB and BTBR strains exhibited low ethanol intakes similar to D2 mice. The addition of 0.2% saccharin to the ethanol solutions significantly increased ethanol intake by most strains and altered the strain distribution pattern. Strong positive correlations (rs ≥ 0.83) were determined between consumption of the unsweetened versus sweetened ethanol solutions. Consumption of saccharin alone was significantly positively correlated with the sweetened ethanol solutions (rs = 0.62–0.81), but the correlation with unsweetened ethanol solutions was considerably lower (rs = 0.37–0.45). These results add new strains to the strain mean database that will facilitate the identification of genetic relationships between voluntary ethanol consumption, saccharin preference, and other phenotypes.     

Effects of glucose and saccharine solutions on subsequent food consumption

Twenty three hr water deprived animals were given access to various glucose and glucose + saccharin solutions during a 1 hr drinking session. Subsequent 1 hr and 22 hr food intakes were measured. Results indicate that more food was consumed during the first post drinking hour by the animals when receiving 3.5% GLU + 0.25% SACC while comparatively less food was consumed by them following the ingestion of 21% GLU and 21% GLU + 0.25% SACC. During the remaining 22 hr when the animals received 21% GLU and 21% GLU + 0.25% SACC they increased their food intake such that total 23 hr food intake was unaffected. Food intake was not related to the amounts of the different fluids consumed but appeared to be determined by other oral and post ingestion factors associated with the different solutions.     

Effects of isolation-rearing on voluntary consumption of ethanol, sucrose and saccharin solutions in Fawn Hooded and Wistar rats

These experiments examined the hypothesis that isolation-rearing and strain influence hedonic mechanisms. In experiment 1, voluntary consumption of ethanol and water was monitored in the home cage of Fawn Hooded (FH) and Wistar rats. FH rats were found to consume more ethanol at low concentrations than Wistar rats, independent of rearing condition, and isolation-reared rats were found to consume more of high ethanol concentrations, independent of strain. In experiment 2, isolation-reared rats were found to consume more sucrose, independent of concentration, than socially reared rats. In experiment 3, Fawn Hooded rats were found to be more sensitive to low concentration solutions of saccharin, and to consume less of the high concentration solutions, while isolation-rearing was found to enhance consumption of high concentrations. Thus, hedonic processes are independently modulated by strain and rearing conditions, although the effects of isolation-rearing appear to be exacerbated in Fawn Hooded rats. Received: 19 August 1997 / Final version: 26 November 1997