Recognizing Axionic Dark Matter by Compton and de Broglie Scale Modulation of Pulsar Timing.

Light axionic dark matter, motivated by string theory, is increasingly favored for the "no weakly interacting massive particle era". Galaxy formation is suppressed below a Jeans scale of ≃10^{8} M_{⊙} by setting the axion mass to m_{B}∼10^{-22} eV, and the large dark cores of dwarf galaxies are explained as solitons on the de Broglie scale. This is persuasive, but detection of the inherent scalar field oscillation at the Compton frequency ω_{B}=(2.5 months)^{-1}(m_{B}/10^{-22} eV) would be definitive. By evolving the coupled Schrödinger-Poisson equation for a Bose-Einstein condensate, we predict the dark matter is fully modulated by de Broglie interference, with a dense soliton core of size ≃150 pc, at the Galactic center. The oscillating field pressure induces general relativistic time dilation in proportion to the local dark matter density and pulsars within this dense core have detectably large timing residuals of ≃400 nsec/(m_{B}/10^{-22} eV). This is encouraging as many new pulsars should be discovered near the Galactic center with planned radio surveys. More generally, over the whole Galaxy, differences in dark matter density between pairs of pulsars imprints a pairwise Galactocentric signature that can be distinguished from an isotropic gravitational wave background.

Towards a classification of biomarkers of neuropsychiatric disease: from encompass to compass.

There is currently considerable imprecision in the nosology of biomarkers used in the study of neuropsychiatric disease. The neuropsychiatric field lags behind others such as oncology, wherein, rather than using 'biomarker' as a blanket term for a diverse range of clinical phenomena, biomarkers have been actively classified into separate categories, including prognostic and predictive tests. A similar taxonomy is proposed for neuropsychiatric diseases in which the core biology remains relatively unknown. This paper divides potential biomarkers into those of (1) risk, (2) diagnosis/trait, (3) state or acuity, (4) stage, (5) treatment response and (6) prognosis, and provides illustrative exemplars. Of course, biomarkers rely on available technology and, as we learn more about the neurobiological correlates of neuropsychiatric disorders, we will realize that the classification of biomarkers across these six categories can change, and some markers may fit into more than one category.

Effects of Preventative Ankle Taping on Planned Change-of-Direction and Reactive Agility Performance and Ankle Muscle Activity in Basketballers.

This study investigated the effects of preventative ankle taping on planned change-of-direction and reactive agility performance and peak ankle muscle activity in basketballers. Twenty male basketballers (age = 22.30 ± 3.97 years; height = 1.84 ± 0.09 meters; body mass = 85.96 ± 11.88 kilograms) with no ankle pathologies attended two testing sessions. Within each session, subjects completed six planned and six reactive randomized trials (three to the left and three to the right for each condition) of the Y-shaped agility test, which was recorded by timing lights. In one session, subjects had both ankles un-taped. In the other, both ankles were taped using a modified subtalar sling. Peak tibialis anterior, peroneus longus (PL), peroneus brevis (PB), and soleus muscle activity was recorded for both the inside and outside legs across stance phase during the directional change, which was normalized against 10-meter sprint muscle activity (nEMG). Both the inside and outside cut legs during the change-of-direction step were investigated. Repeated measures ANOVA determined performance time and nEMG differences between un-taped and taped conditions. There were no differences in planned change-of-direction or reactive agility times between the conditions. Inside cut leg PL nEMG decreased when taped for the planned left, reactive left, and reactive right cuts (p = 0.01). Outside leg PB and soleus nEMG increased during the taped planned left cut (p = 0.02). There were no other nEMG changes during the cuts with taping. Taping did not affect change-of-direction or agility performance. Inside leg PL activity was decreased, possibly due to the tape following the line of muscle action. This may reduce the kinetic demand for the PL during cuts. In conclusion, ankle taping did not significantly affect planned change-of-direction or reactive agility performance, and did not demonstrate large changes in activity of the muscle complex in healthy basketballers. Key pointsAnkle taping using the modified subtalar sling will not affect planned change-of-direction or reactive agility performance as measured by the Y-shaped agility test in healthy male basketball players.Ankle taping using the modified subtalar sling will also generally not affect the activity of the muscles about the ankle. There was some indication for reductions in the activity of the PL in the inside leg of certain cuts.The tape used for the modified subtalar sling may have supported the line of action of the PL, which could reduce the kinetic demand placed on this muscle, and provide a potential fatigue-reducing component for cutting actions.The subtalar sling taping of the ankle in healthy basketball players did not have any adverse effects on the muscle activity of the ankle-foot complex during planned change-of-direction or reactive agility performance tasks.

Training support staff to modify fluids to appropriate safe consistencies for adults with intellectual disabilities and dysphagia: an efficacy study.

BACKGROUND: Modifying the consistency of food and drink is a strategy commonly used in the management of dysphagia for people with intellectual disabilities (ID). People with ID often depend on others for the preparation of food and drink and therefore depend on those caregivers achieving the correct consistency to keep them safe and avoid discomfort during mealtimes. Clinical experience and prior research have demonstrated that although training can improve modification, carers often find modification difficult and potentially stressful and recommend additional support for carers. Fluid consistency is often modified through the addition of powdered thickener. This study investigates the efficacy of typical training and use of consistency guides, the Thickness Indicator Model (TIM) tubes, in helping carers to modify fluids accurately. METHOD: A 3 × 3 pre-post experimental design with a control group was employed to compare the observed accuracy of modification across three groups and at three time points (pre-intervention baseline, immediately post-training intervention and 3-10 months post-training). Sixty-two paid carers who supported people with ID were recruited to participate in the study and each was randomly allocated to one of the three groups: a control group given written guidance only, a group who received typical training and written guidance and a group who received training, written guidance and the TIM tubes. RESULTS & CONCLUSIONS: Typical training resulted in significantly greater carer accuracy in modifying fluid consistencies when compared with written guidance alone. Use of the TIM tubes also significantly improved accuracy in the modification of drinks compared with the group who modified with the aid of written guidance alone. At 3-10-month follow-up only the group who received typical training alongside the TIM tubes were significantly more accurate than the Written Guidance group. Further research is warranted to ascertain the effectiveness of the training and the utility of the TIM tubes in improving accuracy over a longer time scale and in individuals' usual living environments.

The surgical aspects of Role 2 Afloat.

The current configuration of the surgical component of the Role 2 Afloat team is described, including an outline of the equipment available. The lessons learned from a recent exercise, where a Role 2 Afloat team was deployed on RFA CARDIGAN BAY are outlined and expanded, emphasising the difficulties of providing damage control surgery in the maritime environment.

Linking the supersymmetric standard model to the cosmological constant.

String theory has no parameter except the string scale M S , so the Planck scale M Pl, the supersymmetry-breaking scale , the electroweak scale m EW as well as the vacuum energy density (cosmological constant) Λ are to be determined dynamically at any local minimum solution in the string theory landscape. Here we consider a model that links the supersymmetric electroweak phenomenology (bottom up) to the string theory motivated flux compactification approach (top down). In this model, supersymmetry is broken by a combination of the racetrack Kähler uplift mechanism, which naturally allows an exponentially small positive Λ in a local minimum, and the anti-D3-brane in the KKLT scenario. In the absence of the Higgs doublets from the supersymmetric standard model, one has either a small Λ or a big enough , but not both. The introduction of the Higgs fields (with their soft terms) allows a small Λ and a big enough simultaneously. Since an exponentially small Λ is statistically preferred (as the properly normalized probability distribution P(Λ) diverges at Λ = 0+), identifying the observed Λobs to the median value Λ50% yields m EW ∼ 100 GeV. We also find that the warped anti-D3-brane tension has a SUSY-breaking scale ∼ 100 m EW while the SUSY-breaking scale that directly correlates with the Higgs fields in the visible sector is ≃ m EW.

Infection prevention and control in the design of healthcare facilities.

The lead paper, "Healthcare-Associated Infections as Patient Safety Indicators," written by Gardam, Lemieux, Reason, van Dijk and Goel, puts forward the design of healthcare facilities as one of many strategies to improve patient safety with respect to healthcare-associated infections. This commentary explores some of the issues in balancing infection prevention and control priorities with other needs and values brought to the design process. This balance is challenged not only by a lack of supporting evidence but also by the superficial nature in which infection prevention and control are often discussed within a design context. For the physical environment to support any patient safety initiative, the design of the processes must be developed in conjunction with that of the physical environment so that compliance can be natural and convenient. Finally, consideration is given to the value of documenting decision-making related to infection prevention and control in facility design and ongoing assessments of existing facilities.

Anti-mycobacterial therapy in Crohn's disease heals mucosa with longitudinal scars.

BACKGROUND: A possible causative link between Crohn's disease and Mycobacterium avium ss paratuberculosis has been suggested. AIM: To report unique scarring in Crohn's disease patients treated with anti-Mycobacterium avium ss paratuberculosis therapy. PATIENTS: A retrospective review of 52 patients with severe Crohn's disease was conducted. Thirty-nine patients who had at least one follow-up colonoscopy during treatment were included. METHODS: Patients received rifabutin (up to 600 mg/day), clofazimine (up to 100 mg/day) and clarithromycin (up to 1 g/day) - anti-Mycobacterium avium ss paratuberculosis therapy - for 6 months to 9 years. Ramp-up dosing was used. Colonoscopies and histological analyses monitored progress. RESULTS: Twenty-two patients (56.4%, 22/39) healed with unusual scarring, which appeared as branched, ribbon-like, elevated lines. In 2/6 patients (33.3%) who had > 3 years of treatment after scarring occurred, scars receded, becoming imperceptible as full healing occurred. Histologically, a marked reduction in inflammation occurred in 15/39 patients (38.5%). Of these, 6/15 patients (40%) displayed restoration of normal mucosa. Longitudinal scarring occurred in 12/15 patients (80%) with improved histology. CONCLUSIONS: The presence of scarring fading to normal mucosa on anti-MAP therapy implies a more profound healing not seen with standard anti-inflammatory and immunosuppressant drugs. Longitudinal scarring and consequent healing with normal histology should become a standard treatment goal for Crohn's disease.

Hofmeister Anion Effects on Thermodynamics of Caffeine Partitioning between Aqueous and Cyclohexane Phases.

Specific anion effects on the thermodynamics of caffeine partitioning between aqueous and cyclohexane phases were studied in the presence of 11 sodium salts by utilizing UV-vis spectroscopy. It is observed that weakly hydrated anions such as ClO4-, SCN-, and I- salt caffeine into the aqueous phase and increase the standard Gibbs free energy for caffeine transfer. On the other hand, well-hydrated anions such as CO32- and SO42- salt caffeine molecules out of the aqueous solution and promote the transfer process. Results suggest that weakly hydrated anions associate with the hydrophobic patches of caffeine including three methyl groups and a flat heteroatomic ring to solvate caffeine molecules. Well-hydrated anions are excluded from the caffeine surface to salt caffeine molecules out of aqueous solution. Moreover, the enthalpy and entropy of caffeine transfer were obtained by measuring the standard Gibbs free energy for caffeine transfer at varied temperatures. The transfer of caffeine from the aqueous to cyclohexane phase was an endothermic process driven by the entropy of caffeine transfer. However, the trend in standard Gibbs free energy across the Hofmeister series was determined by the enthalpy of caffeine transfer. These results provide an enthalpic origin to explain the Hofmeister trends in aqueous solution.

Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects.

Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 µg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg(-1)) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 µA, 90 µS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation.

Unified selective sorting approach to analyse multi-electrode extracellular data.

Extracellular data analysis has become a quintessential method for understanding the neurophysiological responses to stimuli. This demands stringent techniques owing to the complicated nature of the recording environment. In this paper, we highlight the challenges in extracellular multi-electrode recording and data analysis as well as the limitations pertaining to some of the currently employed methodologies. To address some of the challenges, we present a unified algorithm in the form of selective sorting. Selective sorting is modelled around hypothesized generative model, which addresses the natural phenomena of spikes triggered by an intricate neuronal population. The algorithm incorporates Cepstrum of Bispectrum, ad hoc clustering algorithms, wavelet transforms, least square and correlation concepts which strategically tailors a sequence to characterize and form distinctive clusters. Additionally, we demonstrate the influence of noise modelled wavelets to sort overlapping spikes. The algorithm is evaluated using both raw and synthesized data sets with different levels of complexity and the performances are tabulated for comparison using widely accepted qualitative and quantitative indicators.

Feasibility of investigating differential proteomic expression in depression: implications for biomarker development in mood disorders.

The objective of this study was to determine whether proteomic profiling in serum samples can be utilized in identifying and differentiating mood disorders. A consecutive sample of patients with a confirmed diagnosis of unipolar (UP n=52) or bipolar depression (BP-I n=46, BP-II n=49) and controls (n=141) were recruited. A 7.5-ml blood sample was drawn for proteomic multiplex profiling of 320 proteins utilizing the Myriad RBM Discovery Multi-Analyte Profiling platform. After correcting for multiple testing and adjusting for covariates, growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. In a series of three post hoc analyses correcting for multiple testing, MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls, MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls, and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. Good diagnostic accuracy (ROC-AUC⩾0.8) was obtained most notably for GDF-15, RBP-4 and TTR when comparing BP-I vs controls. While based on a small sample not adjusted for medication state, this discovery sample with a conservative method of correction suggests feasibility in using proteomic panels to assist in identifying and distinguishing mood disorders, in particular bipolar I disorder. Replication studies for confirmation, consideration of state vs trait serial assays to delineate proteomic expression of bipolar depression vs previous mania, and utility studies to assess proteomic expression profiling as an advanced decision making tool or companion diagnostic are encouraged.

Antiparkinsonian efficacy of a novel transdermal delivery system for (+)-PHNO in MPTP-treated squirrel monkeys.

We examined the ability of the antiparkinsonian agent (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) to enter the systemic circulation in therapeutic concentrations after continuous transdermal absorption in squirrel monkeys rendered parkinsonian by MPTP. Direct subcutaneous administration of (+)-PHNO in the dose range of 2.5 to 20 micrograms/kg restored locomotor activity to levels seen in normal monkeys for approximately 1 hour. Application of transdermal patches capable of delivering, into an infinite sink, an estimated 2.6 micrograms/cm2/h of (+)-PHNO over a skin surface area of 4.78 to 19.12 cm2 also restored locomotor activity to the normal range during a 24-hour period. We suggest the use of transdermal application of PHNO as a novel drug delivery system for the improved management of Parkinson's disease.

The novel NK1 receptor antagonist MK-0869 (L-754,030) and its water soluble phosphoryl prodrug, L-758,298, inhibit acute and delayed cisplatin-induced emesis in ferrets.

The anti-emetic profile of the novel brain penetrant tachykinin NK1 receptor antagonist MK-0869 (L-754,030) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluor o)phenyl-4-(3-oxo-1,2,4-triazol-5-yl)methylmorpholine and its water soluble prodrug, L-758,298, has been examined against emesis induced by cisplatin in ferrets. In a 4 h observation period, MK-0869 and L-758,298 (3 mg/kg i.v. or p.o.) inhibited the emetic response to cisplatin (10 mg/kg i.v.). The anti-emetic protection afforded by MK-0869 (0.1 mg/kg i.v.) was enhanced by combined treatment with either dexamethasone (20 mg/kg i.v.) or the 5-HT3 receptor antagonist ondansetron (0.1 mg/kg i.v.). In a model of acute and delayed emesis, ferrets were dosed with cisplatin (5 mg/kg i.p.) and the retching and vomiting response recorded for 72 h. Pretreatment with MK-0869 (4-16 mg/kg p.o.) dose-dependently inhibited the emetic response to cisplatin. Once daily treatment with MK-0869 (2 and 4 mg/kg p.o.) completely prevented retching and vomiting in all ferrets tested. Further when daily dosing began at 24 h after cisplatin injection, when the acute phase of emesis had already become established, MK-0869 (4 mg/kg p.o. at 24 and 48 h after cisplatin) prevented retching and vomiting in three out of four ferrets. These data show that MK-0869 and its prodrug, L-758,298, have good activity against cisplatin-induced emesis in ferrets and provided a basis for the clinical testing of these agents for the treatment of emesis associated with cancer chemotherapy.

The pharmacological properties of the imidazobenzodiazepine, FG 8205, a novel partial agonist at the benzodiazepine receptor.

1. The pharmacological properties of the benzodiazepine receptor ligand, FG 8205 (7-chloro-5,6-dihydro-5-methyl-6-oxo-3-(5-isopropyl-1,2,4-oxadiazol++ +-3-yl)-4H- imidazol[1,5a][1,4]benzodiazepine) have been examined. 2. FG 8205 potently displaced [3H]-flumazenil binding in rat cortical membranes with a Ki of 3.3 nM, but was inactive at 13 neurotransmitter recognition sites. 3. Consistent with a partial agonist profile, the affinity of FG 8205 for the benzodiazepine recognition site was increased in the presence of gamma-aminobutyric acid (GABA, 300 microM) by a degree (-log [IC50 in the presence of GABA/IC50 alone] = 0.34) significantly less than found for diazepam (0.46). FG 8205 also potentiated the inhibitory potency of the GABAA-receptor agonist, isoguvacine, on the hippocampal CA1 population spike and, again, the maximum shift (-log dose-ratio = 0.2) was significantly less than that seen with diazepam (0.4). 4. In anticonvulsant studies, the ED50 doses of FG 8205 and diazepam needed to antagonize seizures induced by pentylenetetrazol (PTZ) or by sound in audiogenic seizure prone mice were similar with values of 0.2-0.3 mg kg-1, i.p. However, even high doses of FG 8205 (50 mg kg-1) did not protect against seizures induced by electroshock. 5. FG 8205 released responding suppressed by footshock in a rat operant conditioned emotional response task over the dose range 0.5-50 mg kg-1 (i.p.). Similar doses of FG 8205 had a marked taming effect in cynomolgus monkeys. However, measures of sedation and ataxia (as measured by rotarod in the mouse, climbing behaviour in the rat, and by scoring arousal and co-ordination in primates) were slight and only transiently affected by FG 8205, and FG 8205 significantly antagonized the rotarod performance deficit induced by diazepam in the mouse. 6. While the potentiation by FG 8205 of the response to isoguvacine in the rat hippocampal slice and the anxiolytic-like effects of the compound in both rats and primates were reversed by the benzodiazepine receptor antagonist, flumazenil, high doses of the antagonist were able only marginally to block the protective effects of FG 8205 against seizures induced by PTZ in the mouse. 7. Thus, FG 8205 does not show the marked motor impairment characteristic of full agonists at the benzodiazepine receptor, consistent with its partial agonist profile in in vitro assay systems. Nevertheless, the compound has sufficient intrinsic activity to maintain high efficacy in anticonvulsant and anxiolytic tests.

Enhanced performance of spatial and visual recognition memory tasks by the selective acetylcholinesterase inhibitor E2020 in rhesus monkeys.

Hepatotoxicity limits the clinical utility of the cholinesterase inhibitor tacrine as a palliative therapy for Alzheimer's disease. The present studies examined the effects of E2020, a selective acetylcholinesterase inhibitor not associated with liver toxicity in man, on cognitive performance in rhesus monkeys using tasks employed previously to evaluate tacrine and other cholinomimetic agents. The ability of E2020 to prevent the induction of a cognitive impairment by the muscarinic receptor antagonist scopolamine was assessed using an automated spatial delayed response task. Coadministration of E2020 (0.5-1.75 mg/kg) caused a dose-dependent reversal of the scopolamine (0.03 mg/kg) induced impairment observed after retention intervals of 10 and 20 s. At the highest dose of E2020 examined (1.75 mg/kg), choice accuracy approached normal control levels. In this dose range, E2020 was well tolerated, but at the higher dose of 2 mg/kg, cholinergic side-effects were apparent. The effect of E2020 on choice accuracy in a visual recognition task was also assessed as this task does not require the use of scopolamine to disrupt performance and beneficial effects of cholinomimetics can therefore be detected at lower doses than in the spatial memory paradigm. In this task, administration of E2020 increased choice accuracy from 59 +/- 1% correct to up to 71 +/- 2% at doses of 0.03 and 0.05 mg/kg. No observable adverse effects were induced by E2020 in this dose range. The ability of E2020 to improve performance in these cognitive tasks resembles the profile of other cholinesterase inhibitors, including tacrine, that also improve cognitive function in Alzheimer's disease patients. Because of its more favourable clinical safety profile, E2020 may provide a significantly improved palliative therapy for dementia.

Drug-induced purposeless chewing: animal model of dyskinesia or nausea?

Drug-induced purposeless chewing movements in rodents are often considered to represent movement disorders or dyskinesias. We have compared the ability of drugs to induce chewing and retching or emesis in squirrel monkeys; such studies are not possible in rodents, which do not vomit. Acute administration of oxotremorine (3.3-33 micrograms/kg IM), SKF38393 (1-30 mg/kg SC) or ipecacuanha (0.5-0.75 mg/kg PO) caused dose-related increases in purposeless chewing which was frequently associated with retching and emesis. Treatment with haloperidol (0.015-0.06 mg/kg IM) did not induce chewing. Rather, haloperidol decreased spontaneous chewing at doses of 0.03 and 0.06 mg/kg. Our findings indicate that at least some drug-induced oral behaviours in rodents may reflect nausea rather than dyskinesia.

Lack of effect of CCKB receptor antagonists in ethological and conditioned animal screens for anxiolytic drugs.

The effects of the CCKB receptor antagonists L-365,260, CI-988 and L-740,093, a new compound with improved bioavailability and CNS penetration, were assessed for anxiolytic-like effects in three rat anxiolytic screens sensitive to benzodiazepines, the elevated plus maze (EPM), conditioned suppression of drinking (CSD) and conditioned emotional response (CER) tests. In the EPM, L-740,093 (0.1-1.0 mg/kg), L-365,260 (0.00001-10.0 mg/kg), and CI-988 (0.01-1.0 mg/kg) did not increase the time spent on the open arms of the maze or the number of entries onto the open arms. In contrast, the benzodiazepine receptor partial agonist, bretazenil (0.3-10.0 mg/kg), significantly increased both the time spent on the open arms and the number of open arm entries. In the CSD and the CER tests, L-740,093 (0.1-1.0 mg/kg) L-365,260 (0.0001-0.1 mg/kg) and CI-988 (0.01-10.0 mg/kg) failed to increase suppression ratios compared to the vehicle-treated control rats, whereas, the benzodiazepine receptor partial agonist FG 8205 (10.0 mg/kg) (CSD) and bretazenil (0.3-3.0 mg/kg) (CER) both significantly increased suppression ratios compared to vehicle-treated control rats. In addition, L-365,260 (1.0-50.0 mg/kg), CI-988 (0.1-10.0 mg/kg) and diazepam (0.1-1.0 mg/kg) were assessed in a squirrel monkey conflict procedure. Although diazepam significantly increased suppressed lever pressing rates, L-365,260 and CI-988 were without effect. The present findings provide little support for the hypothesis that CCKB receptor antagonists have anti-anxiety effects in animals.

Evidence against a specific effect of cholinergic drugs on spatial memory in primates.

A scopolamine-like delay-dependent impairment in spatial delayed response performance in rhesus monkeys was induced by irrelevant interpolated activity or by using extended retention intervals. Physostigmine readily reversed the effects of scopolamine but had no effect on performance in young monkeys performing an irrelevant distractor task or in monkeys tested using extended retention intervals. Reducing stimulus control did not impair performance and did not alter the dose-response curve for induction of a deficit by scopolamine. Reducing the stimulus presentation time impaired performance across all retention intervals in a way which did not resemble the effect of scopolamine and which disappeared with practice. Our findings do not support the proposal that physostigmine interacts specifically with short-term spatial memory in primates.

Blockade of CCK-B receptors by L-365,260 induces analgesia in the squirrel monkey.

The potential antinociceptive effects of the selective cholecystokinin-B (CCK-B) antagonist L-365,260 were examined in the squirrel monkey tail withdrawal test. Pain threshold was measured in 6 male monkeys by recording the latency to remove the tail from a warm (55 degrees C) water bath. L-365,260 at doses of 100 ng/kg to 100 micrograms/kg significantly elevated tail withdrawal latencies throughout a 2 h test period. These data provide the first evidence that blockade of CCK-B receptors induces analgesia in primates.