Anticipation of increasing monetary reward selectively recruits nucleus accumbens.

Comparative studies have implicated the nucleus accumbens (NAcc) in the anticipation of incentives, but the relative responsiveness of this neural substrate during anticipation of rewards versus punishments remains unclear. Using event-related functional magnetic resonance imaging, we investigated whether the anticipation of increasing monetary rewards and punishments would increase NAcc blood oxygen level-dependent contrast (hereafter, "activation") in eight healthy volunteers. Whereas anticipation of increasing rewards elicited both increasing self-reported happiness and NAcc activation, anticipation of increasing punishment elicited neither. However, anticipation of both rewards and punishments activated a different striatal region (the medial caudate). At the highest reward level ($5.00), NAcc activation was correlated with individual differences in self-reported happiness elicited by the reward cues. These findings suggest that whereas other striatal areas may code for expected incentive magnitude, a region in the NAcc codes for expected positive incentive value.

Negative association of neuroticism with brain volume ratio in healthy humans.

BACKGROUND: Brain volume decreases with normal aging. We sought to determine whether, in addition to age, individual differences in stress reactivity (i.e., neuroticism) would also predict reductions in brain volume. METHODS: Brain volume ratios were calculated for a sample of 86 healthy volunteers, based on segmented brain volumes taken from T(1)-weighted magnetic resonance imaging and corrected for intracranial volume. Standardized self-reported measures of dispositional neuroticism were concurrently obtained by administering the Revised NEO Personality Inventory. RESULTS: After statistically controlling for age and sex, neuroticism showed a significant negative association with the ratio of brain to the remainder of the intracranial volume, but was not related to intracranial volume itself. In particular, subfactors of neuroticism related to the chronic experience of arousing negative emotions were associated with reduced brain ratio. CONCLUSIONS: These results suggest that individual differences in stress reactivity contribute to reductions in brain volume observed during adulthood.

Effects of isolation-rearing on locomotion, anxiety and responses to ethanol in Fawn Hooded and Wistar rats.

Voluntary ethanol (EtOH) consumption is increased by isolation-rearing in several rat strains. The following experiments examined the effects of isolation-rearing on basal and ethanol-stimulated behavior in Fawn Hooded rats, an alcohol-preferring rat strain, compared to Wistar rats. Locomotor activity and anxiety were examined under both conditions. Basal locomotor activity was higher in isolated subjects of both strains in low light conditions, but under bright light conditions, this difference was only observed in Wistar rats. Locomotor stimulant effects of EtOH were only observed in isolation-reared rats. In the elevated plus maze, Fawn Hooded rats were more anxious than Wistar rats under low light conditions, but under bright light conditions, Wistar socials were less anxious than all of the other groups. Administration of 1.5 mg/kg EtOH produced an anxiolytic response in the elevated plus maze under bright light conditions in Fawn Hooded rats, but to a lesser degree Wistar rats, particularly Wistar isolates. In conclusion, although both strain and isolation-rearing had effects on locomotion and anxiety as well as the stimulatory and anxiolytic effects of EtOH, these effects appeared to be independent.

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.

Dissociation of reward anticipation and outcome with event-related fMRI.

Reward processing involves both appetitive and consummatory phases. We sought to examine whether reward anticipation vs outcomes would recruit different regions of ventral forebrain circuitry using event-related fMRI. Nine healthy volunteers participated in a monetary incentive delays task in which they either responded to a cued target for monetary reward, responded to a cued target for no reward, or did not respond to a cued target during scanning. Multiple regression analyses indicated that while anticipation of reward vs non-reward activated foci in the ventral striatum, reward vs non-reward outcomes activated foci in the ventromedial frontal cortex. These findings suggest that reward anticipation and outcomes may differentially recruit distinct regions that lie along the trajectory of ascending dopamine projections.

Differential basis of strain and rearing effects on open-field behavior in Fawn Hooded and Wistar rats.

Open-field behavior was examined under several conditions in isolation-reared, and socially reared, Fawn Hooded (FH) and Wistar rats. Lighting conditions (red or white light) and complexity (object or no object) were varied: Experiment 1, white light, no object; Experiment 2, red light, no object; Experiment 3, white light, object; Experiment 4, red light, object. The plasma corticosterone (CORT) response to open-field exposure was examined two further experiments. Observation of differences in open-field behavior, resulting from strain or rearing condition, was dependent on both lighting condition and complexity. Differences in exploratory behavior exhibited by isolation-reared rats were best explained by changes in response to novelty, while those in FH, relative to Wistar, rats were primarily due to increased anxiety. Supporting these conclusions, FH rats had enhanced stimulated CORT levels, while isolation rearing was without effect.

Locomotor-stimulating effects of indirect dopamine agonists are attenuated in Fawn hooded rats independent of postweaning social experience.

The effects of the indirect dopamine (DA) agonists cocaine and D-amphetamine on locomotor activity were examined in Fawn hooded (FH) rats and Wistar rats. The effect of isolation rearing was also examined to determine if it might have different effects in these two strains. Contrary to previous findings in other rat strains, only small increases in locomotor-stimulating responses to low doses of cocaine were observed in the present study as a result of isolation rearing. However, at higher cocaine doses, locomotor activity was substantially attenuated in FH rats relative to Wistar rats. A similar pattern of effects was observed for amphetamine in FH rats but only at the intermediate dose. The effects of strain and rearing were independent. There was no evidence for interactions between these factors.

High-pressure liquid chromatography of amino acids and dipeptides on a tripeptide bonded stationary phase.

A bonded tripeptide (L-valyl-L-phenylalanyl-L-valine) phase has been used as a stationary phase in liquid chromatography. Unique retention orders and retention variations are shown for phenylthiohydantoin (PTH) derivatives of amino acids and isomeric dipeptides using acidic and basic mobile phases. It is shown that the 25 PTH-amino acids studied here have different capacity ratios when 1% citric acid in water (ca. pH 2.5) is used as the mobile phase. The analysis time for these amino acid derivatives could be shortened without a loss in the resolution by adding 5% methanol to the above mobile phase. Of particular importance is the fact that the basic amino acids are eluted first. Isomeric dipeptides have been resolved by using deionized water (pH 5.5), and 1% sodium citrate in water (pH 7.9), as mobile phases. The data show that the nature of the mobile phases, the pH, and the ionic strength are the important factors affecting the selectivity and efficiency of the separations of amino acids and dipeptides.

Nonaqueous reverse phase liquid chromatographic determination of vitamin D2 in multivitamin tablets, using vitamin D3 as internal standard.

The technique of nonaqueous reverse phase chromatography has been successfully applied to the separation of lipophilic vitamins D2 and D3. Separation is achieved with a Zorbax-ODS column and a mobile phase of 10% methanol in acetonitrile. A predetermined amount of vitamin D3 internal standard is added to a portion of a powered tablet sample, which is then extracted and partitioned with a mixture of dimethyl sulfoxide, water, methanol, and hexane. A portion of the hexane extract is concentrated, and purified by passing it through a disposable silica cartridge to remove interfering materials. The method should also be applicable to formulations containing vitamin D3 where vitamin D2 can then be used as the internal standard. A system suitability test is included in the method.

Determination of degradation products and impurities of amoxicillin capsules using ternary gradient elution high-performance liquid chromatography.

A specific high-performance liquid chromatography method has been developed for the determination of amoxicillin penicilloic acids (PA), p-hydroxyphenylglycine (p-HPG), 6-aminopenicillanic acid (6-APA) and unidentified materials in amoxicillin capsules. The accuracy of the measurements was demonstrated by the standard addition technique on actual capsule samples. Within-day and between-day precision studies gave coefficients of variation of 3.15 and 1.70% for PA, 4.75 and 3.81% for p-HPG, and 5.59 and 32.23% for 6-APA, respectively. Typical calibration and expanded linearity of response curves for these components show no curvature over the range of interest. The detection limits for PA, p-HPG and 6-APA are 0.7, 0.2 and 0.6 micrograms/ml of sample extract and are considered adequate for the intended use of the method. These levels correspond to 0.35, 0.10, 0.30 mg per 500-mg Amoxil capsule, respectively.

Effects of 5,7-dihydroxytryptamine depletion of tissue serotonin levels on extracellular serotonin in the striatum assessed with in vivo microdialysis: relationship to behavior.

Effects of i.c.v. administration of 5,7-dihydroxytryptamine (5,7-DHT) on biochemistry and behavior were studied in awake Sprague-Dawley rats. It was found that 5,7-DHT depletion of striatal tissue levels of serotonin (5-HT) does not diminish extracellular levels until substantial depletions occur. This finding is similar to those observed after 6-hydroxydopamine lesions of the brain dopamine systems. Although varying amounts of 5,7-DHT produced serotonin depletions in striatal tissue, decreases in extracellular levels were only observed at tissue depletions greater than 60% compared to saline-injected control subjects. Thus, the effects of serotonin lesions which produce only moderate depletions may not be the result of decreased extracellular serotonin, but instead may be the result of compensatory changes in remaining neurons which maintain normal extracellular serotonin concentrations. Different degrees of striatal serotonin depletion were associated with opposite behavioral effects. Moderate levels of serotonin depletion (50-75%) produced evidence of increased anxiety, while these effects were no longer seen in rats with more severe 5-HT depletions (>75%).

Evaluation of 3-ethoxy-1,2,4-dithiazoline-5-one (EDITH) as a new sulfurizing reagent in combination with labile exocyclic amino protecting groups for solid-phase oligonucleotide synthesis.

3-ethoxy-1,2,4-dithiazoline-5-one (EDITH) was recently introduced as an efficient sulfurizing reagent for solid-phase oligonucleotide synthesis. The successful syntheses were performed using standard base protecting groups (i.e. benzoyl for A and C, isobutyryl for G), which required deprotection in concentrated ammonium hydroxide at 55 degrees C for 15-18 h. We have explored the possibility of using EDITH in combination with fast deprotection chemistry(e.g. Expedite Chemistry using tert -butylphenoxy acetyl as a base protecting group). Surprisingly, poor synthesis performance was observed when syntheses were conducted with EDITH, Expedite Chemistry and standard synthesis cycle (i.e. Coupling-Thio-Cap). Potential G modification seemed to be the source of incompatibility since sequences containing no G or carrying isobutyryl- protected G residues could be synthesized with high efficiency. However, the deleterious G modification can be readily eliminated by inserting a capping step before the sulfurization reaction. Oligomers prepared with the Coupling-Cap-Thio-Cap cycle contained few phosphodiester contaminants as measured by31P-NMR, anion-exchange HPLC and MALDI-TOF mass spectrometry. In addition to reducing deprotection time, this new combination also provides a mild method for the preparation of certain phosphorothioate oligomers that may be sensitive to prolonged ammonia treatment (e.g. thioated RNAs).