Biomedical subjects

D N Jones

Publications and source records attributed to D N Jones.

At least 37 records · Page 2Linked to original sources

PubMed2000

Practical and theoretical issues in gene-targeting studies and their application to behaviour.

Some of the major practical and theoretical issues that are associated with gene-targeting studies in mice are discussed. The availability of sufficient space to house the extensive breeding colonies associated with studies in gene-manipulated mice is an important logistical consideration that requires consideration at an early stage. A practical example is discussed which illustrates some of these issues. Problems associated with disease control and methods of maintaining the health status of valuable colonies are also outlined. Differences in the behavioural phenotype of inbred mouse strains pose important issues for study design and selection of host mouse lines. The results from studies exploring variations in the behavioural phenotype of six common inbred strains are briefly outlined. The impact of phenotypic variation on behavioural studies is considered and the implications for experimental design are discussed.

Animals↗

PubMed2000

Pharmacological actions of a novel, high-affinity, and selective human dopamine D(3) receptor antagonist, SB-277011-A.

SB-277011-A (trans-N-[4-[2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolininecarboxamide), is a brain-penetrant, high-affinity, and selective dopamine D(3) receptor antagonist. Radioligand-binding experiments in Chinese hamster ovary (CHO) cells transfected with human dopamine D(3) or D(2 long) (hD(3), hD(2)) receptors showed SB-277011-A to have high affinity for the hD(3) receptor (pK(i) = 7.95) with 100-fold selectivity over the hD(2) receptor and over 66 other receptors, enzymes, and ion channels. Similar radioligand-binding data for SB-277011-A were obtained from CHO cells transfected with rat dopamine D(3) or D(2). In the microphysiometer functional assay, SB-277011-A antagonized quinpirole-induced increases in acidification in CHO cells overexpressing the hD(3) receptor (pK(b) = 8.3) and was 80-fold selective over hD(2) receptors. Central nervous system penetration studies showed that SB-277011-A readily entered the brain. In in vivo microdialysis studies, SB-277011-A (2. 8 mg/kg p.o.) reversed the quinelorane-induced reduction of dopamine efflux in the nucleus accumbens but not striatum, a regional selectivity consistent with the distribution of the dopamine D(3) receptor in rat brain. SB-277011-A (2-42.3 mg/kg p.o.) did not affect spontaneous locomotion, or stimulant-induced hyperlocomotion. SB-277011-A (4.1-42.2 mg/kg p.o.) did not reverse prepulse inhibition deficits in apomorphine- or quinpirole-treated rats, but did significantly reverse the prepulse inhibition deficit in isolation-reared rats at a dose of 3 mg/kg p.o. SB-277011-A (2.5-78. 8 mg/kg p.o.) was noncataleptogenic and did not raise plasma prolactin levels. Thus, dopamine D(3) receptor blockade produces few of the behavioral effects characteristic of nonselective dopamine receptor antagonists. The effect of SB-277011-A on isolation-induced prepulse inhibition deficit suggests that blockade of dopamine D(3) receptors may benefit the treatment of schizophrenia.

Animals↗

PubMed1999

Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains.

Detailed characterisation of six inbred strains of mice commonly used in transgenic and knockout research was carried out using a battery of behavioural tests (SHIRPA) followed by discriminant analysis of the data. In the primary observation screen, DBA/2 mice were relatively irritable and vocalised during handling. C57BL/6 were hyperactive as measured by transfer arousal, arena activity and touch-escape tests. By contrast, C3H were markedly hypoactive, had significantly enhanced grip strength and were also significantly impaired on the visual placing task. In the elevated plus-maze, BALB/c mice showed the highest level of open arm entries and time spent in the open arms, indicating the lowest level of anxiety. There was a clear dissociation of strains on exploratory activity, as measured in the holeboard test and spontaneous locomotor activity (LMA). DBA/2 mice were hyperactive in LMA but demonstrated relatively low levels of holeboard exploration. None of the six strains learnt the water maze spatial learning task particularly well. C57BL/6 and 129/Sv demonstrated most ability and C3H showed no evidence of having acquired the task. The SHIRPA screening battery and discriminant analysis of the data have enabled us to determine the relevant contribution of a number of behavioural measurements to the marked differences in phenotype of mouse strains. These data confirm the importance of carrying out a comprehensive profile in order to accurately characterise the phenotype of gene-targeted and transgenic mice.

Animals↗

PubMed1999

Orexin A activates locus coeruleus cell firing and increases arousal in the rat.

The localization of orexin neuropeptides in the lateral hypothalamus has focused interest on their role in ingestion. The orexigenic neurones in the lateral hypothalamus, however, project widely in the brain, and thus the physiological role of orexins is likely to be complex. Here we describe an investigation of the action of orexin A in modulating the arousal state of rats by using a combination of tissue localization and electrophysiological and behavioral techniques. We show that the brain region receiving the densest innervation from orexinergic nerves is the locus coeruleus, a key modulator of attentional state, where application of orexin A increases cell firing of intrinsic noradrenergic neurones. Orexin A increases arousal and locomotor activity and modulates neuroendocrine function. The data suggest that orexin A plays an important role in orchestrating the sleep-wake cycle.

Animals↗

PubMed1999

Influence of peptide CRF receptor antagonists upon the behavioural effects of human/rat CRF.

The effects of the corticotropin-releasing factor (CRF) receptor antagonists, alpha-helical CRF-(9-41), [D-Phe12,Nle21,38, CalphaMe-Leu37]humanCRF-(12-41) (D-PheCRF-(12-41)) and astressin ([cyclo(30-33)[D-Phe12,Nle21,38,Glu30,Lys33]h umanCRF-(12-41) upon hypophagic and motor activation response to human/ratCRF (h/rCRF) were investigated. All three antagonists (100 microg intracerebroventricular (i.c.v.)) blocked the effects of h/rCRF (1 microg i.c.v.) upon food intake and body weight change in food-deprived rats. In contrast, alpha-helical CRF-(9-41) and astressin (both at 100 microg i.c.v., but not lower doses), but not D-PheCRF-(12-41) (up to 100 microg i.c.v.), blocked h/rCRF (0.3 microg i.c.v.)-induced motor activation in rats in a familiar environment. The ability of D-PheCRF-(12-41) to block CRF-induced hypophagia, but not motor activation, suggests a selective action of this antagonist upon the behavioural effects of centrally administered h/rCRF.

Animals↗

PubMed1999

Intermediate-term outcome of primary digit amputations in patients with diabetes mellitus who have forefoot sepsis requiring hospitalization and presumed adequate circulatory status.

PURPOSE: The intermediate success and outcome of primary forefoot amputations in patients with diabetes mellitus who have sepsis limited to the forefoot and presumed adequate forefoot perfusion, as determined by means of noninvasive methods, was studied. METHODS: Cases of a university hospital-based practice from January 1984 to April 1998 were retrospectively reviewed. Patients included had diabetes mellitus with forefoot sepsis requiring immediate hospitalization for digit amputations who had adequate arterial circulation for healing based on noninvasive and clinical assessment: palpable pedal pulses (29%), "compressible" ankle pressure of 70 mm Hg or higher (48%), pulsatile metatarsal waveforms (67%), and/or toe pressure higher than 55 mm Hg (36%). All patients underwent a primary single- or multiple-digit amputation (through the interphalangeal joint, metatarsal head, or metatarsal shaft). Additional forefoot procedures (debridement, digit amputation) were performed during the follow-up period as needed for persistent or recurrent infection. The main outcome variables were recurrent or persistent foot infection (defined as requiring rehospitalization for antibiotics, wound care, and/or reoperation), the number of repeat operations and hospitalizations for salvage of limbs with recurrent or persistent infections, and time to complete forefoot healing or foot amputation. RESULTS: Ninety-two patients who had diabetes mellitus with 97 forefoot infections comprised the study group. Ninety-seven primary digit amputations (34 through interphalangeal joints, 28 through metatarsal heads, 35 through metatarsal shafts) were performed. The median length of hospital stay was 10 days. There were no operative deaths. The mean follow-up period was 21 months (range, 3 days to 105 months). The primary amputation healed (without persistent infection) in only 38 limbs (39%), at a mean time of 13 +/- 10 weeks. Twenty-three limbs (24%) had not healed the primary amputation without evidence of persistent infection at last follow-up (mean, 12 weeks). Infection persisted in 35 limbs (36%), and infection recurred in 15 of 38 (40%) healed limbs. An average of 1.0 reoperations (range, 0 to 3) and 1.6 rehospitalizations (range, 1 to 4) were involved in salvage attempts in these recurrent/persistent infections. Five persistent and five recurrent infections ultimately healed (mean, 53 weeks). Complete healing was achieved in only 33 of 97 limbs (34%). Twenty-two foot amputations (20 transtibial, two Syme's) were performed (mean, 49 +/- 74 weeks; 20 for persistent infection). Eighteen persistent/recurrent infections remained unhealed at the last follow-up examination (mean, 105 weeks). CONCLUSION: Patients with diabetes mellitus who have sepsis limited to the forefoot requiring acute hospitalization and undergoing primary digit amputations have a high incidence of intermediate-term, persistent, and recurrent infection, leading to a modest rate of limb loss, despite having apparently salvageable lesions and noninvasive evidence of presumed adequate forefoot perfusion.

Adult↗

PubMed1999

Novel multi-dimensional heteronuclear NMR techniques for the study of 13C-O-acetylated oligosaccharides: expanding the dimensions for carbohydrate structures.

Complex carbohydrates have critical roles in a wide variety of biological processes. An understanding of the molecular mechanisms that underlie these processes is essential in the development of novel oligosaccharide-based therapeutic strategies. Unfortunately, obtaining detailed structural information for larger oligosaccharides (> 10 residues) can be exceedingly difficult, especially where the amount of sample available is limited. Here we demonstrate the application of 13C O-acetylation in combination with novel NMR experiments to obtain much of the information required to characterize the primary structure of oligosaccharides. (H)CMe COH-HEHAHA and H(CMe)COH-HEHAHA experiments are presented that use heteronuclear Hartmann-Hahn transfer to correlate the acetyl groups with sugar ring protons in peracetylated oligosaccharides. The in-phase, pure absorption nature of the correlation peaks in these experiments allows measurement of both chemical shifts and, importantly, 1H-1H coupling constants that are used to define the stereochemistry of the sugar ring. The (HCMe)COH and (HCMe)COH-RELAY experiments provide additional methods for obtaining chemical shift assignments for larger oligosaccharides to define the sites of glycosidic linkages from the patterns of acetylation.

Acetylation↗

PubMed1998

Structure-function relationships in side chain lactam cross-linked peptide models of a conserved N-terminal domain of apolipoprotein E.

Bioactive peptides have multiple conformations in solution but adopt well-defined conformations at lipid surfaces and in interactions with receptors. We have used side chain lactam cross-links to stabilize secondary structures in the following peptide models of a conserved N-terminal domain of apolipoprotein E (cross-link periodicity in parentheses): I, H2N-GQTLSEQVQEELLSSQVTQELRAG-COOH (none); III, [sequence; see text] (i to i + 3); IV,[sequence; see text] (i to i + 4); IVa, [sequence, see text] (i to i + 4) (lactams above the sequence, potential salt bridges below the sequence). We previously demonstrated [Luo et al. (1994) Biochemistry 33, 12367-12377; Braddock et al. (1996) Biochemistry 35, 13975-13984] that peptide III, containing lactam cross-links between the i and i + 3 side chains, enhances specific binding of LDL via a receptor other than the LDL-receptor. Peptide III in solution consists of two short alpha helices connected by a non alpha helical segment. Here we examine the hypothesis that the domain modeled by peptide III is one antipode of a conformational switch. To model another antipode of the switch, we introduced two strategic modifications into peptide III to examine structure-function relationships in this domain: (1) the spacing of the lactam cross-links was changed (i to i + 4 in peptides IV and IVa) and (2) peptides IV and IVa contain the two alternative sequences at a site of a possible end-capping interaction in peptide III. The structure of peptide IV, determined by 2D-NMR, is alpha helical across its entire length. Despite the remarkable degree of structural order, peptide IV is biologically inactive. In contrast, peptides III and possibly IVa contain a central interruption of the alpha helix, which appears necessary for biological activity. These and other studies support the hypothesis that this domain is a conformational switch which, to the extent that it models apolipoprotein E itself, may modulate interactions between apo E and its various receptors.

Amino Acid Sequence↗

PubMed1998

High-resolution structure of an archaeal zinc ribbon defines a general architectural motif in eukaryotic RNA polymerases.

BACKGROUND: Transcriptional initiation and elongation provide control points in gene expression. Eukaryotic RNA polymerase II subunit 9 (RPB9) regulates start-site selection and elongational arrest. RPB9 contains Cys4 Zn(2+)-binding motifs which are conserved in archaea and homologous to those of the general transcription factors TFIIB and TFIIS. RESULTS: The structure of an RPB9 domain from the hyperthermophilic archaeon Thermococcus celer was determined at high resolution by NMR spectroscopy. The structure consists of an apical tetrahedral Zn(2+)-binding site, central beta sheet and disordered loop. Although the structure lacks a globular hydrophobic core, the two surfaces of the beta sheet each contain well ordered aromatic rings engaged in serial edge-to-face interactions. Basic sidechains are clustered near the Zn(2+)-binding site. The disordered loop contains sidechains conserved in TFIIS, including acidic residues essential for the stimulation of transcriptional elongation. CONCLUSIONS: The planar architecture of the RPB9 zinc ribbon-distinct from that of a conventional globular domain-can accommodate significant differences in the alignment of polar, non-polar and charged sidechains. Such divergence is associated with local and non-local changes in structure. The RPB9 structure is distinguished by a fourth beta strand (extending the central beta sheet) in a well ordered N-terminal segment and also differs from TFIIS (but not TFIIB) in the orientation of its apical Zn(2+)-binding site. Cys4 Zn(2+)-binding sites with distinct patterns of polar, non-polar and charged residues are conserved among unrelated RNAP subunits and predicted to form variant zinc ribbons.

Amino Acid Sequence↗

PubMed1998

The behavioural effects of corticotropin-releasing factor-related peptides in rats.

The present study determined the behavioural effects of the corticotropin releasing factor (CRF)-related peptides, human/rat CRF (h/rCRF), ovine CRF (oCRF), sauvagine (SAUV), urotensin I (UT) and the recently discovered neuropeptide, rat urocortin (rUCN). All of the peptides dose-dependently increased motor activity in a familiar environment and reduced feeding in hungry rats. There was no apparent relationship between potency/affinity at CRF2 receptors and effects in these two tests. In a comparison of h/rCRF and rUCN upon discrete spontaneous behaviours, both peptides (3.0 microg i.c.v.) increased activity and grooming, induced a fore-paw tremor and reduced the incidence of motionlessness. However, h/rCRF reduced motionlessness to a greater extent and was a more potent inducer of defaecation, weight loss, oral movements and fore-paw tremor than rUCN. In the elevated X maze, both h/rCRF and rUCN (1.0 microg i.c.v.) had anxiogenic-like effects upon behaviour. In contrast, h/rCRF (1.0 microg i.c.v.), but not rUCN (1.0-10 microg i.c.v.) increased the startle response to an acoustic stimulus. In summary, all the CRF-related peptides increased motor activity and reduced feeding in rats in a similar manner and both rUCN and h/rCRF induced anxiogenesis. However, there were some behavioural differences between rUCN and h/rCRF which require further study. Further pharmacological investigation of the role of CRF receptor subtypes requires the use of subtype selective antagonists.

Animals↗

PubMed1997

Recommended standards for reports dealing with lower extremity ischemia: revised version.

Recommended standards for analyzing and reporting on lower extremity ischemia were first published by the Journal of Vascular Surgery in 1986 after approval by the Joint Council of The Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery. Many of these standards have been accepted and are used in the current literature on peripheral arterial occlusive disease. With the passage of time, some oversights, aspects that require clarification, and better modifications have been recognized. This report attempts to correct these shortcomings while reinforcing those recommendations that have proven satisfactory. Explanatory comments are added to facilitate understanding and application. This version is intended to replace the original version.

Acute Disease↗

PubMed1997

1996 Australian radiology workforce report.

A questionnaire was sent to all radiologists in Australia using a mailing list supplied by individual State Workforce subcommittee members. A reply rate of 72% was obtained. There are currently 1061 radiologists (1010.5 full-time equivalents) or 55.5 radiologists per million population, placing Australia in the mid-range compared with other OECD countries. This has increased slightly from 54.1 in 1994. There is a small but definite State variation. Utilizing current trainee numbers and traditional attrition rates, there is no projected change in these figures (55.3 in 2001), but the continued introduction of 'migrant' radiologists is postulated to cause an increase (56.6 with 25 migrants and 58.4 with 50 migrants in 2001). Analysis of work-practice indicates a performance rate of 14,100 procedures per year per practising radiologist. There is again a State variation. It is estimated that the total number of medical imaging procedures per 1000 population per year (rendered by radiologists) is 815. These latter two figures place Australia in the mid-range compared with the United States and Great Britain. General radiography, mammography, ultrasound, and CT are the most common procedures (in that order), and are performed by the largest proportion of radiologists.

Adult↗

PubMed1996

Rational design of novel immunosuppressive drugs: analogues of azathioprine lacking the 6-mercaptopurine substituent retain or have enhanced immunosuppressive effects.

Clinical use of the immunosuppressive drug azathioprine is limited by potentially serious toxic effects related to depression of bone marrow function. The immunosuppressive and toxic properties of azathioprine are regarded as being properties of the cytotoxicity of its metabolite, 6-mercaptopurine (6-MP). However, azathioprine has an immunosuppressive effect additional to that attributable to 6-MP alone, and we propose that this is associated with an action of the methylnitroimidazolyl substituent. This suggests a route to the rational design of nontoxic immunosuppressants by replacing the 6-MP component of azathioprine with nontoxic thiols. We have synthesized and tested in vitro 24 such analogues, with two being further tested in vivo. In the human mixed lymphocyte reaction, virtually all compounds showed some degree of activity, 10 compounds being more active than azathioprine. In vivo, two compounds were more effective than azathioprine at prolonging graft survival in mice. In an oral toxicity study in male CD1 mice at doses equivalent to those at which azathioprine caused severe bone marrow depression both analogues had no toxic effects. Our results show that the immunosuppressive effects and bone marrow toxicity of azathioprine are not a consequence of release of 6-MP alone, and with appropriate modification can be separated, an approach which may lead to less toxic immunosuppressive drugs.

Animals↗

PubMed1996

Pulmonary vasomotor dysfunction is produced with chronically high pulmonary blood flow.

This study examined the hypothesis that chronic high pulmonary blood flow produces dysfunction of the mechanisms of pulmonary vasorelaxation. A 3:1 left-to-right shunt was created in dogs by bilateral femoral artery-femoral vein shunts with use of 6 mm polytetrafluoroethylene grafts. Isolated pulmonary artery rings were studied at the following times: 3 days (n = 2), 2 weeks (n = 4), and 5 months (n = 6). Control animals had no shunt. The following mechanisms of pulmonary vasorelaxation were studied in isolated pulmonary artery rings (4 rings from each dog): (1) endothelium-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), (2) endothelium-independent cyclic guanosine monophosphate-mediated relaxation (response to sodium nitroprusside), and (3) beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol). Statistical analysis was done by analysis of variance. This model of high pulmonary flow did not produce an increase in pulmonary arterial pressure or transpulmonary gradient. However, chronic high pulmonary flow produced progressive dysfunction of all three of these mechanisms of pulmonary vasorelaxation. By 5 months of high pulmonary flow, acetylcholine produced only 36% +/- 6% relaxation versus 95% +/- 5% in control animals (p < 0.05). Likewise, sodium nitroprusside produced only 69% +/- 6% relaxation versus 100% in control animals (p < 0.05). Finally, isoproterenol produced only 55% +/- 5% relaxation versus 94% +/- 6% in control animals (p < 0.05). We conclude that dysfunction of the mechanisms of pulmonary vasorelaxation may contribute to exaggerated perioperative pulmonary vasoconstriction in the setting of chronic high pulmonary blood flow.

Acetylcholine↗

PubMed1996

Monitoring of neoadjuvant therapy response of soft-tissue and musculoskeletal sarcoma using fluorine-18-FDG PET.

UNLABELLED: The purpose of this study was to investigate the potential role of FDG-PET in the monitoring of neoadjuvant therapy of soft-tissue and musculoskeletal sarcomas. METHODS: Nine patients were studied. Neoadjuvant therapy consisted of either chemotherapy or combined radiotherapy and hyperthermia. The FDG-PET studies were obtained, when possible, prior to therapy, 1-3 wk after commencement of therapy, and prior to surgery after completion of neoadjuvant therapy. In two patients, all three studies were completed. The remainder of patients underwent one or two studies at varying timepoints. RESULTS: In tumors treated with combined radiotherapy and hyperthermia, well-defined regions of absent uptake developed within responsive tumors, correlating pathologically with necrosis. Following treatment, a peripheral rim of FDG accumulation was found to correlate pathologically with the formation of a fibrous pseudocapsule. In tumors treated with chemotherapy, FDG accumulation decreased more homogeneously throughout the tumor, in responsive cases. Despite 100% tumor cell kill in some patients, persistent tumor FDG uptake was observed which correlated pathologically with uptake within benign therapy-related fibrous tissue. Significant FDG accumulation was also observed at the site of an uncontaminated incisional biopsy. CONCLUSION: These initial results demonstrate changes in tumor accumulation of FDG during and after neoadjuvant therapy; these changes are dependent on the type of neoadjuvant therapy administered. Prominent FDG accumulation was observed in benign tissues both within and adjacent to the treated tumor.

Adolescent↗

PubMed1996

A computer controlled pulsatile pump: preliminary study.

A Stepper Motor Driven Reciprocating Pump (SDRP) can replace roller pumps and rotary pumps for cardio pulmonary bypass, hemodialysis and regional perfusion. The blood pumping ventricles are basically the same as ventricles used for air driven artificial hearts and ventricular assist devices. The electric stepper motor uses a flexible linkage belt to produce a reciprocating movement, which pushes a hard sphere into the diaphragm of the blood ventricles. The SDRP generates pulsatile flow and has a small priming volume. The preset power level of the motor driver limits the maximum potential outflow pressure, so the driver acts as a safety device. A double pump can be made by connecting two fluid pumping chambers to opposing sides of the motor base. Each pump generates pulsatile flow. Pressure and flow studies with water were undertaken. Preliminary blood studies showed low hemolysis, even when circulating a small amount of blood up to 16 hours.

Animals↗

PubMed1995

HMG-D is an architecture-specific protein that preferentially binds to DNA containing the dinucleotide TG.

The high mobility group (HMG) protein HMG-D from Drosophila melanogaster is a highly abundant chromosomal protein that is closely related to the vertebrate HMG domain proteins HMG1 and HMG2. In general, chromosomal HMG domain proteins lack sequence specificity. However, using both NMR spectroscopy and standard biochemical techniques we show that binding of HMG-D to a single DNA site is sequence selective. The preferred duplex DNA binding site comprises at least 5 bp and contains the deformable dinucleotide TG embedded in A/T-rich sequences. The TG motif constitutes a common core element in the binding sites of the well-characterized sequence-specific HMG domain proteins. We show that a conserved aromatic residue in helix 1 of the HMG domain may be involved in recognition of this core sequence. In common with other HMG domain proteins HMG-D binds preferentially to DNA sites that are stably bent and underwound, therefore HMG-D can be considered an architecture-specific protein. Finally, we show that HMG-D bends DNA and may confer a superhelical DNA conformation at a natural DNA binding site in the Drosophila fushi tarazu scaffold-associated region.

Animals↗

PubMed1995

Effect of scopolamine on visual attention in rats.

In the present study, the effects of scopolamine (SCOP) were determined upon the performance of rats in the five-choice serial reaction time task, a test of attention analogous to the continuous performance test in man. Rats were trained to detect and respond to brief flashes of light presented randomly in one of five locations until a stable level of performance was reached. SCOP (0.03-0.1 mg/kg SC) was administered 30 min prior to testing under standard conditions of stimulus presentation. SCOP reduced response accuracy at the highest dose and dose-dependently increased omissions and perseverative responses. However, these effects were mimicked by scopolamine methylbromide (SCOPMBr) which might suggest a peripheral site of action. When the task difficulty was increased by manipulating the stimulus presentation parameters, i.e. reduced stimulus intensity, duration or temporal predictability, SCOP (0.075 mg/kg SC) failed further to impair performance accuracy. However, in two separate experiments, SCOP (0.075 mg/kg SC) robustly increased the distractibility caused by a burst of loud white-noise occurring unpredictably during the intertrial-interval: SCOP significantly decreased accuracy and increased omissions, magazine latency, premature and perseverative responses compared with vehicle and the equivalent dose of SCOPMBr. These findings provide further evidence of a role for the central cholinergic system in attention.

Animals↗