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Acute tolerance is a rapid decrease in the effect of alcohol relative to the blood alcohol concentration (BAC) occurring within the duration of a single dose of alcohol. It remains uncertain which cognitive domains are susceptible to acute tolerance, because findings vary between tasks used to measure the effect of alcohol. This study examined acute tolerance in subjective intoxication and in 2 cognitive domains: information processing, measured using the Inspection Time Task (ITT), and response inhibition, measured with the Sustained Attention to Response Task (SART). Forty participants were allocated to either an alcohol or placebo group. After baseline measures, the alcohol group were given an active dose to produce a peak BAC of 0.07%, whereas the placebo group received a placebo beverage. ITT and SART performance were measured at a BAC of 0.05% twice during the course of the dose, once when BAC was ascending and again when descending. The placebo group was tested at equivalent times. When BAC was ascending, the alcohol group showed increased ratings of subjective intoxication and impaired performance on the ITT. Consistent with an acute tolerance effect, ratings of subjective intoxication and impairment on the ITT in the alcohol group were lower when BAC was descending. Performance on the SART was not found to be affected by alcohol. The findings suggest information processing is a domain of behavior that shows acute tolerance to alcohol and that the subjective intoxication felt at a BAC of 0.05% can decrease substantially within the duration of a single dose. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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Although the strength of the effect produced by alcohol is generally dose dependent, its effect on behavior cannot be reliably predicted by the dose alone because the dose effect has been shown to vary. Acute behavioral tolerance is a rapid decrease in the dose effect of alcohol, seen to occur within the duration of a single dose. Numerous research paradigms have been used to examine acute behavioral tolerance, across an array of different behavioral measures. We have reviewed studies that used a research paradigm appropriate to test for acute behavioral tolerance. The primary aim was to examine the different paradigms that have been used to identify what empirical evidence of the effect has been found. The additional aims were to identify domains of behavior in which acute tolerance has been shown to occur and ascertain which conditions have been shown to influence it. Findings of acute tolerance were prevalent. Seven different research paradigms were identified, and each found evidence of acute behavioral tolerance in at least 1 study. The effect was not uniform across all behavioral measures. Subjective measures reliably showed the effect, but objective measures of behavior were less reliable, providing evidence that particular aspects of task performance are more sensitive to acute tolerance than others. The dose effect of alcohol for behavioral measures is often shown to decrease within the duration of a single dose. Investigations into, and considerations of, the effects of alcohol on behavior need to consider temporal changes in the dose effect. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

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BACKGROUND AND PURPOSE: This study aimed to investigate the relationship between the plasma concentration (PK) of the novel histamine H3 receptor antagonist, GSK239512, and the brain occupancy of H(3) receptors (RO) in healthy human volunteers. EXPERIMENTAL APPROACH: PET scans were obtained after i.v. administration of the H(3) -specific radioligand [(11) C]GSK189254. Each subject was scanned before and after single oral doses of GSK239512, at 4 and 24 h after dose. PET data were analysed by compartmental analysis, and regional RO estimates were obtained by graphical analysis of changes in the total volumes of distribution of the radioligand, followed by a correction for occupancy by the high affinity radioligand. The PK/RO relationship was analysed by a population-modelling approach, using the average PK of GSK239512 during each scan. KEY RESULTS: Following administration of GSK239512, there was a reduction in the brain uptake of [(11) C]GSK189254 in all regions, including cerebellum. RO at 4 h was higher than at 24 h, and the PK/RO model estimated a PK associated with 50% of RO of 0.0068 ng·mL(-1) . This corresponds to a free concentration of 4.50 × 10(-12 ) M (pK = 11.3). CONCLUSIONS AND IMPLICATIONS: The affinity of GSK239512 for brain H3 receptors in humans in vivo is much higher than that expected from studies in vitro, and higher than that observed in PET studies in pigs. The study illustrates the utility of carrying out PET studies in humans early in drug development, providing accurate quantification of GSK239512 RO in vivo as a function of time and dose.

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The development of an enzyme-linked immunoassay (ELISA) for the adipokinetic neuropeptide hormone, Pya-AKH, from the firebug Pyrrhocoris apterus L. is described. The ELISA measures as little as 20 fmol of Pya-AKH. Tested against a range of synthetic peptides, the assay has a high sensitivity for peptides containing the C-terminal motif FTPNWamide. The amounts of Pya-AKH in the brain, corpora cardiaca, suboesophageal ganglia, and fused thoracic and abdominal ganglionic mass are very small, with only the corpora cardiaca containing appreciable levels of the hormone (ca. 4 pmol per bug). Preliminary estimates of the persistence of the hormone in the haemolymph are consistent with values determined for AKHs in other insects, and suggest that Pya-AKH has a rapid turnover with a half-life of ca. 18 min. Measurements of circulating titres of AKH in Pyrrhocoris are only possible in the ELISA described here by using pooled samples of haemolymph, and after preliminary clean-up of the haemolymph samples. The titre of Pya-AKH in resting reproductive female Pyrrhocoris is ca. 1 fmol/&mgr;l.

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It has been suggested that cooperative interactions between antifreeze proteins (AFPs) on the ice surfaces are required for complete inhibition of ice crystal growth. To test this hypothesis, a 7-kDa type III AFP was linked through its N-terminus to thioredoxin (12 kDa) or maltose-binding protein (42 kDa). The resultant 20-kDa and 50-kDa fusion proteins were larger in diameter than free AFP and thus precluded any extensive AFP-AFP contacts on the ice surface. Both fusion proteins were at least as active as free AFP at virtually all concentrations tested. By these criteria, AFPs function independently of each other and do not require specific intermolecular interactions to bind tightly to ice.

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