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R Raymond

Publications and source records attributed to R Raymond.

At least 19 recordsLinked to original sources
PubMed2006

Assessing the welfare of genetically altered mice.

In 2003, under the auspices of the main UK funders of biological and biomedical research, a working group was established with a remit to review potential welfare issues for genetically altered (GA) mice, to summarize current practice, and to recommend contemporary best practice for welfare assessments. The working group has produced a report which makes practical recommendations for GA mouse welfare assessment and dissemination of welfare information between establishments using a 'mouse passport'. The report can be found at www.nc3rs.org.uk/GAmice and www.lal.org.uk/gaa and includes templates for the recommended welfare assessment scheme and the mouse passport. An overview is provided below.

Animal Husbandry↗
PubMed2005

Decreased adenosine receptor binding in dystonic brains of the dt(sz) mutant.

In patients with paroxysmal non-kinesigenic dyskinesias, episodes of dystonia can be provoked by stress and also by methylxanthines (e.g. caffeine), which inhibit adenosine A(1)/A(2A) receptors. In the dt(sz) mutant hamster, a model of this movement disorder, adenosine A(1) receptor antagonists were previously found to worsen dystonia, while adenosine A(1) and A(2A) receptor agonists exerted pronounced beneficial effects. Therefore, in the present study, adenosine receptor A(1) and A(2A) binding was determined by autoradiographic analyses in dt(sz) hamsters under basal conditions, i.e. in the absence of a dystonic attack, and in a group of mutant hamsters which exhibited severe stress-induced dystonic attacks prior to kill. In comparison with non-dystonic control hamsters, [(3)H]DPCPX (8-cyclopentyl-1,3-dipropylxanthine) binding to adenosine A(1) receptors and [(3)H]CGS 21680 (2p-(2carboxyethylphen-ethylamino-5'-N-ethlycarboxamindoadenosine) binding to adenosine A(2A) receptors were significantly lower throughout the brain of dystonic animals. Under normal resting conditions, mutant hamsters showed significant decreases in adenosine A(1) (-12 to-42%) and in A(2A) (-19 to-34%) receptor binding compared with controls. Stressful stimulation increased adenosine A(1) and A(2A) receptor binding in almost all brain regions in both control and dystonic hamsters. The stress-induced increase was more marked in mutant hamsters, leading to a disappearance of differences in most regions compared with stimulated controls, except the striatum. In view of previous findings of striking beneficial effects of adenosine A(1) and A(2A) receptor agonists and of striatal dysfunctions in the dt(sz) mutant, the reduced adenosine receptor binding may be an important factor in the pathogenesis of paroxysmal dystonia.

Animals↗
PubMed2004

Altered expression of preproenkephalin and prodynorphin mRNA in a genetic model of paroxysmal dystonia.

The dtsz mutant hamster represents a model of primary paroxysmal dystonia, in which dystonic episodes occur in response to stress. Previous examinations demonstrated striatal dysfunctions in dtsz hamsters. In the present study, in situ hybridization was used to examine preproenkephalin and prodynorphin expression as potential indices of imbalances between the striatopallidal and striatonigral pathways. Brain analyses were performed in dtsz hamsters under basal conditions, i.e., in the absence of dystonia, as well as mutant hamsters that exhibited severe stress-induced dystonic attacks immediately prior to sacrifice. In the striatum the basal expression of prodynorphin tended to be higher, while that of preproenkephalin tended to be lower in mutant hamsters in comparison to non-dystonic control hamsters. Significant basal changes were restricted to higher levels of prodynorphin in the ventrolateral striatum and lower prodynorphin and preproenkephalin mRNA expression in the hippocampus and/or in subregions of the hypothalamus. After stressful stimulation, the neuropeptides increased in several regions in both animals groups. In comparison to stimulated control hamsters, a significantly lower prodynorphin expression was found in several limbic areas of stimulated mutant hamsters during the manifestation of dystonia, while preproenkephalin mRNA was significantly lower in the anterior and dorsal striatal subregions and in nucleus accumbens. Since changes in the expression of these opioid peptides have been suggested to be related to abnormal dopaminergic activity, the present findings may reflect disturbances in striatal dopaminergic systems, and also in limbic structures in the dtsz mutant, particularly during the expression of dystonia.

Analysis of Variance↗
PubMed2002

Changes in AMPA receptor binding in an animal model of inborn paroxysmal dystonia.

Previous pharmacological studies suggested that glutamatergic overactivity contributes to manifestation of dystonic attacks in mutant hamsters (dt(sz)), a model of idiopathic paroxysmal dystonia in which episodes of dystonia occur in response to stress. In the present study, [(3)H]AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor binding was determined by autoradiographic analyses in 41 brain (sub)regions of dt(sz) hamsters under basal conditions, i.e., in the absence of dystonia, and in a group of mutant hamsters that exhibited severe stress-induced dystonic attacks immediately prior to sacrifice. In comparison to nondystonic control hamsters the basal [(3)H]AMPA binding was significantly higher in the ventromedial and ventrolateral caudate putamen, the anterior cingulate cortex, the hippocampus, and the lateral septum of dystonic brains. During dystonic attacks the [(3)H]AMPA binding was significantly lower in the dorsomedial, dorsolateral, and posterior caudate putamen; the ventromedial thalamus; and the frontal cortex of mutant hamsters compared with control animals that were exposed to the same external stimulation. The basal increase in AMPA receptor density within limbic structures may contribute to the susceptibility of stress-inducible dystonic episodes in mutant hamsters. Since AMPA receptor activation is known to cause a fast reduction of the affinity and an internalization of postsynaptic AMPA receptors, the latter finding could reflect a glutamatergic overactivity within the striato-thalamo-cortical circuit during the expression of dystonia, which is in line with previous neurochemical and pharmacological data in dt(sz) hamsters.

Animals↗
PubMed2002

Regional decreases in NK-3, but not NK-1 tachykinin receptor binding in dystonic hamster (dt(sz)) brains.

Although the pathophysiology of primary dystonias is currently unknown, it is thought to involve changes in the basal ganglia-thalamus-cortex circuit, particularly activity imbalances between direct and indirect striatal pathways. Substance P, a member of the tachykinin family of neuropeptides, is a major component in the direct pathway from striatum to basal ganglia output nuclei. In the present study quantitative autoradiography was used to examine changes in neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptors in mutant dystonic hamsters (dt(sz)), a well characterized model of paroxysmal dystonia. NK-1 receptors were labeled in 10 dystonic brains and 10 age-matched controls with 3 nM [(3)H]-[Sar(9), Met(O(2))(11)]-SP. NK-3 binding sites were labeled in adjacent sections with 2.5 nM [(3)H]senktide. NK-1 binding was found to be unaltered in 27 brain areas examined. In contrast, NK-3 binding was significantly reduced in layers 4 and 5 of the prefrontal (-46%), anterior cingulate (-42%) and parietal (-45%) cortices, ventromedial thalamus (-42%) and substantia nigra pars compacta (-36%) in dystonic brains compared to controls. The latter effects may be particularly relevant in view of evidence that activation of NK-3 receptors on dopaminergic neurons in the substantia nigra pars compacta can increase nigrostriatal dopaminergic activity. Since previous studies indicated that a reduced basal ganglia output in mutant hamsters is based on an overactivity of the direct pathway which also innervates substantia nigra pars compacta neurons, the decreased NK-3 binding could be related to a receptor down-regulation. The present finding of decreased NK-3 receptor density in the substantia nigra pars compacta, thalamic and cortical areas substantiates the hypothesis that disturbances of the basal ganglia-thalamus-cortex circuit play a critical role in the pathogenesis of paroxysmal dystonia.

Animals↗
PubMed2001

Anti-interleukin-6 antibodies attenuate inflammation in a rat meningitis model.

OBJECTIVES: Interleukin-6 (IL-6) is elevated in the cerebrospinal fluid (CSF) of humans and animals with bacterial meningitis. This study's hypothesis was that anti-IL-6 antibodies will attenuate meningeal inflammation in a rat model of bacterial meningitis. METHODS: 14 male Sprague-Dawley rats were inoculated intracisternally (IC) with 0.1 mL of heat-killed pneumococci. At one hour post-inoculation, the rats received intraperitoneal doses of either 1.0 mL phosphate-buffered saline (PBS treatment group, n = 7) or 70 microg anti-IL-6 antibodies in 1.0 mL PBS (anti-IL-6 antibody treatment group, n = 7). Nine rats (normal group, n = 9) had no inoculation, and four rats (surgical sham group, n = 4) had IC inoculations of saline. At six hours post-inoculation, all the animals had CSF removed via IC tap. The CSF protein and white blood cell (WBC) count measures were compared using a t-test. RESULTS: Mean CSF WBC for the anti-IL-6 treatment group was 2,458/microL, versus the PBS controls' mean of 9,697/microL (p = 0.007). Mean CSF protein for the anti-IL-6 group was 180 mg/dL, versus 296 mg/dL for the controls (p = 0.032). The surgical sham and normal animals had normal CSF WBC and protein values. CONCLUSIONS: In this rat meningitis model, systemic treatment with anti-IL-6 antibodies after the induction of meningitis suppressed both CSF WBC count and CSF protein level, two important indices of meningeal inflammation.

Animals↗
PubMed2000

A large rubella outbreak with spread from the workplace to the community.

CONTEXT: Childhood vaccination has reduced rubella disease to low levels in the United States, but outbreaks continue to occur. The largest outbreak in the past 5 years occurred in Nebraska in 1999. OBJECTIVES: To examine risk factors for disease, susceptibility of the risk population, role of vaccine failure, and the need for new vaccination strategies in response to the Nebraska rubella outbreak. DESIGN, SETTING, AND PATIENTS: Investigation of 83 confirmed rubella cases occurring in Douglas County, Nebraska, between March 23 and August 24, 1999; serosurvey of 413 pregnant women in the outbreak locale between October 1998 and March 1999 (prior to outbreak) and April and November 1999 (during and after outbreak). MAIN OUTCOME MEASURES: Case characteristics, compared with that of the general county population; area childhood rubella vaccination rates; and susceptibility among pregnant women before vs during and after the outbreak. RESULTS: All 83 rubella cases were unvaccinated or had unknown vaccination status and fell into 3 groups: (1) 52 (63%) were young adults (median age, 26 years), 83% of whom were born in Latin American countries where rubella vaccination was not routine. They were either employed in meatpacking plants or were their household contacts. Attack rates in the plants were high (14.4 per 1000 vs 0. 19 per 1000 for general county population); (2) 16 (19%), including 14 children (9 of whom were aged <12 months) and 2 parents, were US-born and non-Hispanic, who acquired the disease through contacts at 2 day care facilities (attack rate, 88.1 per 1000); and (3) 15 (18%) were young adults (median age, 22 years) whose major disease risk was residence in population-dense census tracts where meatpacking-related cases resided (R(2) = 0.343; P<.001); 87% of these persons were born in Latin America. Among pregnant women, susceptibility rates were 13% before the outbreak and 11% during and after the outbreak. Six (25%) of 24 susceptible women tested were seropositive for rubella IgM. Rubella vaccination rates were 90.2% for preschool children and 99.8% for school-aged children. CONCLUSIONS: A large rubella outbreak occurred among unvaccinated persons in a community with high immunity levels. Crowded working and living conditions facilitated transmission, but vaccine failure did not. Workplace vaccination could be considered to prevent similar outbreaks. JAMA. 2000;284:2733-2739.

Adolescent↗
PubMed2000

Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment and in subjects requiring hemodialysis.

Two open-label studies assessed the pharmacokinetics of single orally administered doses of 40 mg of stavudine in subjects with renal impairment. In one study (study I), 15 subjects with selected degrees of renal impairment, but not requiring hemodialysis, were stratified into three groups of five subjects each according to creatinine clearance (CL(CR)) normalized by body surface area (ml/min/1.73 m(2)): mild (CL(CR), 60 to 80), moderate (30 to 50), and severe (</=20) renal impairment. Five healthy subjects (CL(CR) >/= 90) were also enrolled. The stavudine area under the curve from 0 h to infinity (AUC(0-infinity)) increased nonlinearly with declining renal function: 1,864, 2,215, 3,609, and 5,928 ng. h/ml for normal renal function and for mild, moderate, and severe renal impairment, respectively (P = 0.0001 between renal impairment groups). The following stavudine dosage recommendations for renal impairment were proposed for subjects weighing >/=60 kg: CL(CR) of >50 ml/min/1.73 m(2), 40 mg every 12 h; CL(CR) of 21 to 50 ml/min/1. 73 m(2), 20 mg every 12 h; and CL(CR) of 10 to 20 ml/min/1.73 m(2), 20 mg every 24 h. For subjects weighing <60 kg, the proposed doses were 30, 15, and 15 mg, respectively, with the same dosing intervals specified above. In a second study (study II), 12 subjects with end-stage renal disease requiring hemodialysis three times a week were enrolled in a randomized, open-label crossover study (dialysis 2 h after dosing and lasting 4 h or dosing without dialysis). There were no statistically significant differences for AUC(0-infinity), AUC(2-6), time to maximum concentration of drug in serum, half-life, or apparent oral clearance when the two treatment dosage regimens were compared. As a result of study II, the recommended dosing rate for subjects requiring hemodialysis was the same as that proposed for those with severe renal impairment not requiring hemodialysis; however, dosing was recommended to follow hemodialysis and to occur at the same time each day.

Administration, Oral↗
PubMed2000

Unexpected mortality reduction with abciximab for in-stent restenosis.

Treatment of in-stent restenosis is generally considered low risk, and it is not clear if adjunctive use of abciximab is beneficial in this low-risk population. We determined the effect of adjunctive abciximab during percutaneous coronary intervention (PCI) for treatment of in-stent restenosis. Two hundred and ninety-three patients with in-stent restenosis underwent PCI at the Cleveland Clinic between January 1996 and December 1998. Patients undergoing directional atherectomy, laser treatment and brachytherapy were excluded (9 patients). Of the remaining 284, seventy-nine patients received abciximab during PCI and 205 were treated without abciximab. The groups were similar with respect to age, gender, left ventricular function, number of vessels involved, history of prior coronary artery bypass grafting and unstable symptoms at presentation. There were more diabetics, hypertensives, and patients with elevated cholesterol in the abciximab-treated group. At 1-year follow-up, there was a significantly lower incidence of myocardial infarction (2.5% versus 5.3%; p < 0.05) and lower mortality (1.2% versus 5.8%; p < 0.01) in the abciximab-treated group. There was no difference in the incidence of revascularization. The findings of a lowered mortality and myocardial infarction rate with abciximab warrants further prospective study in patients with in-stent restenosis.

Abciximab↗
PubMed1999

Immediate increase in benzodiazepine binding in rat brain after a single brief experience in the plus maze: a paradoxical effect.

A single drug-free experience in the elevated plus-maze is well documented to reduce the behavioral effects of benzodiazepines (BZs) in subsequent tests. To ascertain the possible role of altered BZ receptor binding to in this phenomenon, rats received a 5-min exposure to the elevated plus maze and were immediately sacrificed. Receptor autoradiography revealed that [3H]flunitrazepam binding was significantly elevated in several amygdaloid and hippocampal nuclei (range: 13-23%); [3H]muscimol binding in adjacent sections was not significantly altered. These results suggest that BZ receptors can change very rapidly in response to anxiogenic conditions. However, the unexpected finding that [3H]flunitrazepam binding is increased by maze exposure suggests that the subsequent loss of BZ anxiolytic effects in the plus-maze is probably unrelated to alterations in BZ binding in brain.

Amygdala↗
PubMed1999

Acute stress increases thyroid hormone levels in rat brain.

BACKGROUND: In experimental animals, exposure to uncontrollable stress induces a number of behavioral and biochemical changes that resemble symptoms seen in human depression and other psychiatric conditions. The present study used a yoked design to examine the effects of uncontrollable footshock stress on brain thyroid hormones in male and female rats. METHODS: Animals in one group received 15 trials where footshock could be terminated by pressing a lever (escapable shock). Rats in a second group received the same amount of shock, but had no control over shock termination (inescapable shock). Control rats received no shock. RESULTS: No significant differences were found among the three groups, for either males or females, in whole brain levels of thyroxine (T4) 3 hours after the footshock session. In contrast, significant group differences in brain levels of triiodothyronine (T3) were found for both males and females. In males, brain T3 was elevated by 21% in the inescapable shock group when compared to controls (p < .012). In females, brain T3 increased by 19% in the escapable shock group when compared to controls (p < .026). Plasma levels of both T3 and T4 were at control levels for all groups. CONCLUSIONS: These results provide the first demonstration that brain T3 levels change rapidly in response to acute stress. The data further suggest that the effects of stress controllability on brain T3 levels may be different for males and females.

Acute Disease↗
PubMed1999

Tyrosine hydroxylase immunoreactivity and [3H]WIN 35,428 binding to the dopamine transporter in a hamster model of idiopathic paroxysmal dystonia.

Recent pharmacological studies and receptor analyses have suggested that dopamine neurotransmission is enhanced in mutant dystonic hamsters (dt(sz)), a model of idiopathic paroxysmal dystonia which displays attacks of generalized dystonia in response to mild stress. In order to further characterize the nature of dopamine alterations, the present study investigated possible changes in the number of dopaminergic neurons, as defined by tyrosine hydroxylase immunohistochemistry, as well as binding to the dopamine transporter labelled with [3H]WIN 35,428 in dystonic hamsters. No differences in the number of tyrosine hydroxylase-immunoreactive neurons were found within the substantia nigra and ventral tegmental area of mutant hamsters compared to non-dystonic control hamsters. Similarly, under basal conditions, i.e. in the absence of a dystonic episode, no significant changes in [3H]WIN 35,428 binding were detected in dystonic brains. However, in animals killed during the expression of severe dystonia, significant decreases in dopamine transporter binding became evident in the nucleus accumbens and ventral tegmental area in comparison to controls exposed to the same external stimulation. Since stimulation tended to increase [3H]WIN 35,428 binding in control brains, the observed decrease in the ventral tegmental area appeared to be due primarily to the fact that binding was increased less in dystonic brains than in similarly stimulated control animals. This finding could reflect a diminished ability of the dopamine transporter to undergo adaptive changes in response to external stressful stimulation in mutant hamsters. The selective dopamine uptake inhibitor GBR 12909 (20 mg/kg) aggravated dystonia in mutant hamsters, further suggesting that acute alterations in dopamine transporter function during stimulation may be an important component of dystonia in this model.

Animals↗
PubMed1999

Effect of endotoxin shock on the clearance of lidocaine and indocyanine green in the perfused rat liver.

Endotoxin administration and cecal ligation and puncture produce significant hepatocellular dysfunction when studied in vivo. Specific factors that are present in vivo after endotoxin administration and cecal ligation and puncture, such as alterations in liver blood flow, circulating mediators, and hypoxia, can alter hepatic function. In this study, we used an isolated perfused liver to evaluate the effects of in vivo administration of endotoxin on hepatic function using indocyanine green (ICG) as a global marker of function and lidocaine and its metabolite, MEGX, as specific markers of the CYP450 enzyme system. Endotoxin (Escherichia coli; 45 mg/kg i.p.) was administered to rats followed by a 6-h monitoring before preparation of the isolated in situ perfused liver. Livers from control and endotoxin groups received either ICG (control, n = 6; endotoxin, n = 5) or lidocaine (control, n = 8; endotoxin, n = 8). A separate group of rats (n = 6) received cimetidine (an inhibitor of the CYP450 enzyme system) at a dose of 80 mg/kg daily for 3 days. Livers were perfused via the portal vein by using a single-pass system with a balanced salt solution 6 h after receiving either endotoxin or saline or 24 h after receiving the last dose of cimetidine. After a 40-min stabilization period, ICG or lidocaine was infused via the portal vein until steady-state concentrations were reached in the venous outflow. The total hepatic clearance and intrinsic hepatic clearance for ICG and lidocaine were unchanged in the livers obtained from endotoxin-treated rats. This model could adequately detect CYP450 inhibition because cimetidine-treated rats had significantly lower initial MEGX concentrations (0.63 +/- 0.03 mg/L) compared with control (0.77 +/- 0.03 mg/L) and endotoxin-treated (0.74 +/- 0.04 mg/L) rats. Septic livers had significantly higher initial hepatic oxygen consumption (HVO2) than did control livers (45 +/- 3 microL/min/g vs 82 +/- 9 microL/min/g). The HVO2 remained higher in the septic livers and significantly increased throughout the study, which demonstrated that the livers remained viable and functional. These data indicate that there is no detectable hepatocellular dysfunction after endotoxin shock using ICG, lidocaine, and MEGX in the isolated perfused liver; therefore the dysfunction reported from in vivo studies may be reversible when the liver is removed from the shocked environment.

Anesthetics, Local↗
PubMed1998

Efficacy and safety of a hemostatic puncture closure device with early ambulation after coronary angiography. Angio-Seal Investigators.

A collagen hemostatic puncture closure device has been developed as an alternative to traditional manual pressure techniques for achieving effective femoral arterial hemostasis after coronary angiography. The purpose of the current study was to determine if patients receiving this device can ambulate safely at 1 hour compared with patients receiving traditional manual pressure and bed rest after sheath removal for diagnostic cardiac catheterization. Patients (n = 304) were randomized to either the device group (n = 202) with ambulation at 1 hour after sheath removal or to the manual pressure control group (n = 102) with ambulation at 4 to 6 hours after sheath removal. The device group achieved earlier time to hemostasis (0.9 +/- 3 vs 17.0 +/- 8 minutes, p = 0.0001) and faster time to outpatient discharge (5.0 +/- 4 vs 7.7 +/- 4 hours, p = 0.0001) compared with the control group. There were bleeding or vascular complications in 19 patients (9%) in the device group and in 6 patients (6%) in the manual pressure group (p = 0.397). In patients undergoing diagnostic coronary angiography, this device, compared with traditional techniques for achieving hemostasis after sheath removal, allows for faster time to effective hemostasis with resultant earlier discharge from the hospital.

Aged↗
PubMed1998

Regional alterations in neuronal activity in dystonic hamster brain determined by quantitative cytochrome oxidase histochemistry.

The neural mechanisms underlying idiopathic dystonia are currently unknown. Genetic animal models, such as the dt(sz) hamster, a model of idiopathic paroxysmal dystonia, may be helpful to providing insights into the pathophysiology of this common movement disorder. Recent metabolic mapping studies in the hamster model, using 2-deoxyglucose autoradiography, demonstrated altered 2-deoxyglucose uptake in motor areas such as the striatum, ventral thalamic nuclei, red nucleus, and deep cerebellar nuclei, during dystonic attacks. Whereas the 2-deoxyglucose method is thought to reflect mainly acute alterations of synaptic activity, determination of cytochrome oxidase activity has been suggested as a method of choice to examine sustained baseline changes in neuronal activity. Therefore, in the present study quantitative cytochrome oxidase histochemistry was used to identify chronic regional alterations in the absence of dystonic attacks in mutant hamsters. For comparison with recent 2-deoxyglucose studies, cytochrome oxidase activity was also determined during a dystonic attack, which was induced by mild stress. Cytochrome oxidase was determined in 109 brain regions of dystonic hamsters and non-dystonic, age-matched control hamsters. In the absence of a dystonic attack, a tendency to decreased cytochrome oxidase activity was found in most brain regions, possibly due to retarded brain development in mutant hamsters. Significant decreases in cytochrome oxidase activity were found in motor areas and limbic structures, such as hippocampus, piriform cortex, fundus striatum, globus pallidus, substantia nigra pars reticulata, mediodorsal nucleus of the thalamus, ventral pallidum, and interpositus nucleus of the cerebellum. After induction of a dystonic attack, the trend of decreased cytochrome oxidase activity disappeared, except in globus pallidus and interpositus nucleus of the cerebellum. Although the significant alterations in cytochrome oxidase activity in the absence of a dystonic attack were moderate, the data are in line with previous findings in the mutant hamsters, indicating that dysfunctions of the basal ganglia and their output nuclei are involved in the dystonic condition. Altered neural activity in limbic structures, found in the absence of dystonic attacks in mutant hamsters, may contribute to the stress-susceptibility of the animals.

Animals↗
PubMed1998

Heterogeneous effects of rapid eye movement sleep deprivation on binding to alpha- and beta-adrenergic receptor subtypes in rat brain.

Quantitative receptor autoradiography was used to map alterations in binding to alpha1-, alpha2-, beta1- and beta2-adrenergic receptors throughout the brain of rats deprived of rapid eye movement sleep for 96 h. Binding of [3H]prazosin to alpha1 sites, while not significantly different in any of 46 brain regions examined, showed a clear overall tendency towards decreased values after sleep deprivation. [3H]UK-14,314-labeled alpha2 binding sites were not significantly affected by sleep deprivation in any of 91 brain regions analysed, despite a trend towards increased values. In contrast, beta-adrenergic binding was significantly reduced throughout the brain. Binding to beta1 sites labeled by [125I]iodopindolol in the presence of ICI-11855 was significantly reduced in 13 of 69 brain areas examined; binding to beta2 sites labeled by [125I]iodopindolol in the presence of CGP-20712A was likewise reduced throughout the brain and significantly so in 25 of the 72 brain areas analysed. Rank ordering of the binding changes indicated that reductions in beta1 vs beta2 binding were maximal in different brain areas. This pattern of results may reflect a particular configuration of effects specifically associated with sleep loss stress. The results are consistent with evidence of persisting noradrenergic cell activity during sleep deprivation. The observed heterogeneity of effects suggests that not all norepinephrine receptors are equally affected by rapid eye movement sleep deprivation.

Animals↗