Publications du CHU de Rouen recensées
 dans MEDLINE / PubMed en février 2009 (N = 17)

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1: PLoS ONE. 2009;4(2):e4596. Epub 2009 Feb 25.

In very young infants severity of acute bronchiolitis depends on carried viruses.

Marguet C, Lubrano M, Gueudin M, Le Roux P, Deschildre A, Forget C, Couderc L,
Siret D, Donnou MD, Bubenheim M, Vabret A, Freymuth F.

Respiratory Diseases, Allergy and CF Unit, Pediatric Department, Rouen University
Hospital Charles Nicolle, Rouen, France. christophe.marguet@chu-rouen.fr

BACKGROUND: RT amplification reaction has revealed that various single viruses or
viral co-infections caused acute bronchiolitis in infants, and RV appeared to
have a growing involvement in early respiratory diseases. Because remaining
controversial, the objective was to determine prospectively the respective role
of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very
young infants. METHODS AND PRINCIPAL FINDINGS: 209 infants (median age: 2.4
months) were enrolled in a prospective study of infants <1 year old, hospitalized
for a first episode of bronchiolitis during the winter epidemic season and with
no high risk for severe disease. The severity was assessed by recording SaO(2)%
at admission, a daily clinical score (scale 0-18), the duration of oxygen
supplementation and the length of hospitalization. Viruses were identified in
94.7% by RT amplification reaction: RSV only (45.8%), RV only (7.2%), hMPV only
(3.8%), dual RSV/RV (14.3%), and other virus only (2%) or coinfections (9%). RV
compared respectively with RSV and dual RSV/RV infection caused a significant
less severe disease with a lower clinical score (5[3.2-6] vs. 6[4-8], p = 0.01
and 5.5[5-7], p = 0.04), a shorter time in oxygen supplementation (0[0-1] days
vs. 2[0-3] days, p = 0.02 and 2[0-3] days, p = 0.03) and a shorter hospital stay 
(3[3-4.7] days vs.6 [5-8] days, p = 0.001 and 5[4-6] days, p = 0.04). Conversely,
RSV infants had also longer duration of hospitalization in comparison with RSV/RV
(p = 0.01) and hMPV (p = 0.04). The multivariate analyses showed that the type of
virus carried was independently associated with the duration of hospitalization. 
CONCLUSION: This study underlined the role of RV in early respiratory diseases,
as frequently carried by young infants with a first acute bronchiolitis. RSV
caused the more severe disease and conversely RV the lesser severity. No
additional effect of dual RSV/RV infection was observed on the severity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19240806 [PubMed - in process]

2: Histopathology. 2009 Feb;54(3):319-27.

Down-regulated expression of the TSAP6 protein in liver is associated with a
transition from cirrhosis to hepatocellular carcinoma.

Caillot F, Daveau R, Daveau M, Lubrano J, Saint-Auret G, Hiron M, Goria O, Scotte
M, Francois A, Salier JP.

Inserm Unité 905 and Institut Fédératif de Recherches Multidisciplinaires sur les
Peptides, Faculté de Médecine-Pharmacie, Centre Hospitalier Universitaire, Rouen,
France. frederique.caillot@etu.univ-rouen.fr

AIMS: Hepatocellular carcinoma (HCC) results from cirrhosis and, in Western
Europe, hepatitis C virus and alcoholism are the predominant causes of this
disease. We recently documented a global transcript repression in hepatocarcinoma
nodules. The tumour suppressor activated pathway-6 (TSAP6) transcript codes for a
transmembrane molecule that is an inducer of a caspase-3-dependent apoptotic
pathway. The down-regulation of TSAP6 transcripts in HCC and perinodular
cirrhosis, which contrasts with a sustained transcript level in HCC-free
cirrhosis, has suggested that this hepatic protein level may provide a prognostic
marker for HCC occurrence. METHODS AND RESULTS: This protein was quantified by
semiquantitative assessment of immunohistochemistry on samples from 42 cases
HCC-free cirrhosis, 49 cases cirrhosis with HCC, 43 HCC associated with healthy
liver and 31 controls. TSAP6 expression was linked to the liver state, healthy or
cirrhotic without or with an HCC and to tumour grade. CONCLUSIONS: With biopsies 
periodically performed for surveillance purposes, the decreased expression of
TSAP6 in cirrhotic tissue could reflect a decrease in the apoptotic process and
could be interpreted as a warning sign. This evaluation of the TSAP6 level in
cirrhotic liver conveys predictive information for the development of HCC.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19236508 [PubMed - in process]

3: Eur J Neurol. 2009 Feb 19. [Epub ahead of print]

Anatomy of executive deficit following ruptured anterior communicating artery
aneurysm.

Martinaud O, Perin B, Gérardin E, Proust F, Bioux S, Gars DL, Hannequin D,
Godefroy O.

Department of Neurology, Rouen University Hospital, Rouen, France.

Background and purpose: To evaluate behavioral and cognitive deficits following
anterior communicating artery aneurysm rupture and determine critical lesion
locations. Methods: We investigated 74 patients with standardized cognitive tests
and behavioral inventory. Two examiners rated MRI signal abnormalities in 51
predetermined regions of interest. Classification tree analysis was used to
select regions associated with each cognitive deficit. Results: Eleven patients
presented behavioral executive deficits and 10 had cognitive executive deficit.
Their presence depended on left hemisphere lesions only: (i) ventral striatum
lesion was associated with behavioral executive deficit (P = 0.04), reduction of 
activities (P = 0.01), and hyperactivity (P = 0.02); (ii) superior frontal gyrus 
lesion, with cognitive executive deficit (P = 0.01), action initiation deficit (P
= 0.02), and rule deduction deficit (P = 0.02); (iii) anterior half of centrum
semiovale lesion, with Stroop inhibition deficit (P = 0.02); (iv) medial superior
and middle frontal gyri lesions, with task coordination deficit (P = 0.01); and
(v) middle frontal gyrus lesion, with words generation deficit (P = 0.02).
Conclusion: This study supports that (i) cognitive executive deficits depend
mostly on lateral prefrontal lesions, (ii) with locations varying according to
executive process, and (iii) behavioral executive deficits are mainly due to left
ventral striatum lesion in post-aneurysmal damage.

PMID: 19236465 [PubMed - as supplied by publisher]

4: Purinergic Signal. 2009 Feb 21. [Epub ahead of print]

Characterisation of the R276A gain-of-function mutation in the ectodomain of
murine P2X7.

Adriouch S, Scheuplein F, Bähring R, Seman M, Boyer O, Koch-Nolte F, Haag F.

Inserm U905, 76183, Rouen, France, sahil.adriouch@univ-rouen.fr.

The cytolytic P2X7 purinoceptor is widely expressed on leukocytes and has sparked
interest because of its key role in the activation of the inflammasome, the
release of the pro-inflammatory cytokine IL-1beta and cell death. We report here 
the functional characterisation of a R276A gain-of-function mutant analysed for
its capacities to induce membrane depolarisation, calcium influx and opening of a
large membrane pore permeable to YO-PRO-1. Our results highlight the particular
sensitivity of R276A mutant to low micromolar adenosine triphosphate (ATP)
concentrations, which possibly reflect an increased affinity for its ligands, and
a slower closing kinetics of the receptor channel. Our findings support the
notion that evolutionary pressures maintain the low sensitivity of P2X7 to ATP.
We also believe that the R276A mutant described here may be useful for the
generation of new animal models with exacerbated P2X7 functions that will serve
to better characterise its role in inflammation and in immune responses.

PMID: 19234763 [PubMed - as supplied by publisher]

5: Gynecol Obstet Fertil. 2009 Feb 20. [Epub ahead of print]

[Statistics in medicine: Mann and Whitney test.]

[Article in French]

Roman H.

PHU, clinique gynécologique et obstétricale, CHU de Rouen, 1, rue de Germont,
76031 Rouen, France.

Publication Types: 
    LETTER

PMID: 19233706 [PubMed - as supplied by publisher]

6: Int Urogynecol J Pelvic Floor Dysfunct. 2009 Feb 17. [Epub ahead of print]

Experimental biomechanical evaluation of polypropylene prostheses used in pelvic 
organ prolapse surgery.

Sergent F, Desilles N, Lacoume Y, Bunel C, Marie JP, Marpeau L.

Clinique Gynécologique et Obstétricale, CHU-Hôpitaux de Rouen, 1 rue de Germont, 
76031, Rouen Cedex, France, Fabrice.Sergent@chu-rouen.fr.

INTRODUCTION AND HYPOTHESIS: Although polypropylene (PP) is the most common
biomaterial used to repair genital prolapse via vaginal route, its mechanical
properties however remain obscure. METHODS: An abdominal hernia rabbit model was 
used to evaluate retraction, solidity, and elasticity of the principal types of
PP prostheses currently available, i.e., three large pore size monofilament
prostheses, one heavy weight (HWPP), a second low weight (LWPP), and a third
coated with atelocollagen (CPP). A small pore size multifilament PP (MPP) implant
was also tested. RESULTS: In comparison with HWPP (12%), LWPP (15%), and MPP
(30%), CPP had less retraction (8% of the original size). Unlike pore size,
weight prosthesis is not an influencing factor for retraction. Atelocollagen
coating reduced retraction. HWPP and MPP were the most solid prostheses. MPP
supported the greatest elastic force. CONCLUSIONS: When the biomechanical
parameters were comparatively assessed, HWPP was considered to have the most
advantageous properties for prolapse surgery.

PMID: 19221679 [PubMed - as supplied by publisher]

7: Arch Dermatol. 2009 Feb;145(2):157-62.

Risk factors for the development of ocular complications of Stevens-Johnson
syndrome and toxic epidermal necrolysis.

Gueudry J, Roujeau JC, Binaghi M, Soubrane G, Muraine M.

Department of Ophthalmology, Hôpital Charles Nicolle, 1 rue de Germont, 76031
Rouen, France. julie.gueudry@chu-rouen.fr

OBJECTIVES: To describe the acute and late ocular manifestations of toxic
epidermal necrosis (TEN), Stevens-Johnson syndrome (SJS), and overlap syndrome
and to identify predictors for the development of ocular complications. DESIGN:
Retrospective cohort study. SETTING: A single referral unit in a university
hospital. PATIENTS: The study included 159 patients (mean [SD] age, 49.9 [19.8]
years) with TEN and SJS during an 8-year period. Forty-nine patients were
contacted at least 15 months after hospital discharge. MAIN OUTCOME MEASURES:
Records were reviewed for demographics, cause of the condition, and severity of
ocular involvement. The patients were contacted to assess late ocular
complications. RESULTS: A total of 117 patients (74%) had acute ocular
involvement, which was mild in 58%, moderate in 8%, and severe in 8%. Patients
with TEN had more frequent (odds ratio [OR], 2.7; 95% confidence interval [CI],
1.06-6.90; P = .05) but not more severe (OR, 0.95; 95% CI, 0.20-4.5; P = .99)
acute ocular involvement. Forty-nine patients were contacted at least 15 months
after hospital discharge, and 63% had late ocular complications. Dry eye syndrome
was the most common. The mean (SD) Ocular Surface Disease Index score was 32.9
(30.3) (range, 0-97.5). The severity of the acute ocular disease was found to be 
the only significant risk factor of late complications (P = .002), even though 5 
patients without acute ocular involvement developed dry eye syndrome.
CONCLUSIONS: Ocular involvement is common in patients with SJS and TEN. Late
complications are more frequent in patients with severe initial eye involvement
but may also develop in patients without patent initial ocular symptoms.

PMID: 19221260 [PubMed - in process]

8: Presse Med. 2009 Feb 11. [Epub ahead of print]

[Ventilatory support at home: Indications of oxygen therapy and non invasive
ventilation.]

[Article in French]

Muir JF, Lamia B, Molano C, Cuvelier A.

Service de Pneumologie et Unité de Soins Intensifs Respiratoires, CHU de Rouen,
F-76031 Rouen Cedex, France.

The main indication of LTO is COPD with chronic respiratory failure, where it
improves life expectancy. By extension, LTO may be proposed to other etiologies
of CRF with chronic documented hypoxemia. Daily duration is at least 15H per day.
Non invasive ventilation (NIV) represents facial or nasal ventilation. Consensus 
indications of NIV are restrictive pulmonary diseases (chest wall and /or
parenchmal sequelae, neuromuscular diseases, or obesity hypoventilation syndrome)
Real role of NIV in log-term management of COPD remains controversial.

PMID: 19217250 [PubMed - as supplied by publisher]

9: Eur Respir J. 2009 Feb 12. [Epub ahead of print]

Human in-vivo fluorescence microimaging of the alveolar ducts and sacs during
bronchoscopy.

Thiberville L, Salaün M, Lachkar S, Dominique S, Moreno-Swirc S, Vever-Bizet C,
Bourg-Heckly G.

Rouen, F-76000 France; and Faculté de Médecine-Pharmacie, Rouen, F-76000 France; 
LITIS EA 4108 (groupe Quant-IF), Rouen, F-76000 France.

To assess fibered confocal fluorescence microscopy (FCFM) as a tool to image the 
alveolar respiratory system in-vivo during bronchoscopy.A 488 nm excitation
wavelength FCFM device was used in 41 healthy subjects including 17 active
smokers. After topical anesthesia, the 1.4 mm miniprobe was introduced into the
bronchoscope working channel and advanced distally to the alveoli. Morphometric
and cellular analyses were performed on selected frames harboring a minimal
compression effect.In-vivo acinar microimaging was obtained from each lung
segment except for the apical and posterior segments of both upper lobes.
Reproducible patterns, corresponding to the elastic framework of the axial and
peripheral interstitial systems, were recorded from 192 separate acini. The mean 
thickness of the acinar elastic fibers was 10+/-2.5 microm. Alveolar mouth
diameters (mean 278+/-53 microm) were normally distributed but appeared smaller
in the right upper lobe and right medial basal segment (p<0.001). Lobular
microvessels (median diameter 90 microm) were equally distributed throughout the 
lungs. Alveolar macrophages were not detectable in non-smokers, whereas a
specific tobacco-tar induced fluorescence was observed in smoking subjects,
providing fine details of the alveolar walls and macrophages. A strong
correlation was found between the number of cigarettes smoked per day and the
amount of large and mobile macrophages observed in-vivo, as well as with the
intensity of the macrophage alveolitis.FCFM enables to accurately explore the
peripheral lung in-vivo in both smokers and non smokers.

PMID: 19213792 [PubMed - as supplied by publisher]

10: Gynecol Obstet Fertil. 2009 Feb 3. [Epub ahead of print]

[All-safe and/or all-humane childbirth?]

[Article in French]

Marpeau L.

Clinique gynécologique et obstétricale, hôpital Charles-Nicolle, CHU de Rouen, 1,
rue de Germont, 76031 Rouen cedex, France.

PMID: 19195920 [PubMed - as supplied by publisher]

11: Gynecol Obstet Fertil. 2009 Feb 3. [Epub ahead of print]

[Infectious spondylodiscitis after a laparoscopic sacrocolpopexy: About one
case.]

[Article in French]

Descargues G, Bouzouita A, Grise P.

Centre de pelvipérinéologie, clinique Saint-Hilaire, 2, place Saint-Hilaire,
76000 Rouen, France; Service d'urologie, CHU Charles-Nicolle, 1, rue de Germont, 
76000 Rouen, France.

One case of spondylodiscitis, over a period of 18 months after a laparoscopic
sacrocolpopexy with suture, was reported. After a needle aspiration of the
disco-vertebral space retrieving Pseudomonas, adapted antibiotic treatment and
immobilization permit favorable evolution. The clinical, biological and imaging
with MRI favorable evolution, prompted not to disassemble the prosthetic
material, however this option should be discussed at the outset when large
abscess or vaginal fistula or unfavorable evolution with medical treatment.
Fixation promontory must interest the prevertebral ligament and not the disc;
using suture should be preferred to staples.

PMID: 19195918 [PubMed - as supplied by publisher]

12: Int J Obstet Anesth. 2009 Feb 3. [Epub ahead of print]

Anaesthesia mode for caesarean section and mortality in very preterm infants: An 
epidemiologic study in the EPIPAGE cohort.

Laudenbach V, Mercier FJ, Rozé JC, Larroque B, Ancel PY, Kaminski M, Bréart G,
Diemunsch P, Subtil D, Lejus C, Fresson J, Arnaud C, Rachet B, Burguet A,
Cambonie G; Epipage study group.

Department of Neonatology and Pediatric Intensive Care & EA 4309 NeoVasc Research
Group, Rouen Institute for Biomedical Research, University of Rouen, Rouen,
France.

BACKGROUND: Little is known about the influence of anaesthesia for caesarean
section on outcome in very preterm infants. METHODS: A prospective,
population-based, cohort study (the EPIPAGE cohort) included all births before 33
weeks in nine French regions in 1997. Of 2360 infants live-born between 27 and 32
weeks, 1338 were delivered by caesarean section with general anaesthesia (n=711, 
53.1%), spinal anaesthesia (n=419, 31.3%), or epidural anaesthesia (n=208,
15.6%). Neonatal mortality was compared among these three groups using bi-
(according to gestational age and to anaesthetic technique) and multivariate
analyses. RESULTS: Neonatal mortality was 10.1% with general anaesthesia, 12.2%
with spinal anaesthesia and 7.7% with epidural anaesthesia. After adjustment for 
gestational age and characteristics of pregnancy, delivery and neonate, spinal
anaesthesia was associated with a higher risk of neonatal death than general
anaesthesia (adjusted odds ratio, 1.7; 95% confidence interval 1.1 to 2.6).
CONCLUSION: In this population-based study, spinal anaesthesia was associated
with an increased risk of neonatal mortality in very preterm infants compared to 
general anaesthesia (and epidural anaesthesia), independently from gestational
age and characteristics of the pregnancies, deliveries and neonates. Although
this multivariate analysis does not prove a causal relationship, the results
suggest it could exist, particularly if maternal haemodynamics are poorly
controlled. With recent significant change in the conduct of spinal anaesthesia, 
further studies are needed to investigate potential harmful effects of
anaesthesia on very preterm infants delivered by caesarean section.

PMID: 19195873 [PubMed - as supplied by publisher]

13: Rev Med Interne. 2009 Feb 3. [Epub ahead of print]

[Drug-associated tendon disorders: After fluoroquinolones ... here are statins!]

[Article in French]

Marie I, Noblet C.

Département de médecine interne, CHU de Rouen, 147, avenue du Marechal-Juin,
76031 Rouen cedex, France.

PMID: 19195746 [PubMed - as supplied by publisher]

14: Pathol Biol (Paris). 2009 Feb;57(1):71-5. Epub 2009 Jan 20.

[Efficacy of a multidisciplinary team for preventing hospital acquired invasive
aspergillosis: A five years experience.]

[Article in French]

Etancelin P, Silly S, Merle V, Bonmarchand G, Richard JC, Vannier JP, Nouvellon
M.

Laboratoire d'hygiène hospitalière, institut de biologie clinique, CHU de Rouen, 
1, rue de Germont, 76031 Rouen, France.

Invasive hospital-acquired aspergillosis (IA) is responsible for lethal
outbreaks. In 2002, an interdisciplinary team was created in the teaching
hospital of Rouen in order to organize the surveillance of construction sites by 
the implementation of environmental measures of prevention. The aim of our study 
was to estimate the efficiency of these measures using an indirect indicator,
reflecting the incidence of the cases of invasive nosocomial aspergillosis (AI): 
the consumption of antifungals. From the nominative prescriptions established, we
studied the medical files about 210 patients to track down the number of IA cases
in intensive care unit (ICUI) and in pediatric hematology-oncology units between 
2002 and 2006. The incidence of the cases was put in parallel with the various
periods of level 5-risk works during these five years. The relative risk of
appearance of the disease was calculated. In pediatric haematology-oncology unit,
35 cases were diagnosed on 99 medical files which have been studied and in ICU 19
cases were classified on 93 studied files. The follow-up of the incidence in both
units stake in parallel with the periods of level 5-risk works does not show
increase of the number of cases. The calculated relative risk indicates the same 
result: the level 5-risk works are not a factor facilitating the appearance of
invasive aspergillosis cases. This study shows the importance of the
environmental measures of prevention during the periods of works within services 
for risk. The coordination of the actors within an interdisciplinary cell seems
thus essential for the prevention of AIN.

Publication Types: 
    English Abstract

PMID: 19157722 [PubMed - in process]

15: Presse Med. 2009 Feb;38(2):303-16. Epub 2008 Dec 11.

[Infections in polymyositis and in dermatomyositis]

[Article in French]

Marie I.

Département de Médecine Interne, CHU Rouen, F-76031 Rouen Cedex, France.
isabelle.marie@chu-rouen.fr

Infections result in increased mortality rates in patients with
polymyositis/dermatomyositis, leading to death in 9 to 30% of cases. The
following parameters can be considered of predictive value for infection onset in
polymyositis/dermatomyositis: age, lymphopenia, esophageal dysfunction,
ventilatory insufficiency, interstitial lung disease, calcinosis cutis, as well
as higher mean daily doses of steroids. A great variety of microorganisms may be 
responsible for pyogenic and opportunistic infections in
polymyositis/dermatomyositis. Opportunistic infections are more often due to
mycobacteria and fungi (Pneumocystis jiroveci, Candidasp.). Because a great
variety of microorganisms may be responsible for opportunistic infections, it
seems difficult to initiate primary prophylaxis in patients with
polymyositis/dermatomyositis who exhibit risk factors for opportunistic
infections. Primary prophylaxis of Pneumocystis jirovecipneumonia should be given
in the group of patients exhibiting CD4-cell count lower than 250/mm(3).
Vaccination should be performed in patients with polymyositis/dermatomyositis,
prior to immunosuppressive therapy institution.

Publication Types: 
    English Abstract

PMID: 19084369 [PubMed - in process]

16: Int J Androl. 2009 Feb;32(1):57-65. Epub 2007 Oct 11.

Impact level of dihydrotestosterone on the hypothalamic-pituitary-leydig cell
axis in men.

Cailleux-Bounacer A, Rohmer V, Lahlou N, Lefebvre H, Roger M, Kuhn JM.

Department of Endocrinology and Clinical Investigation Center INSERM 0204,
University of Rouen, Bois Guillaume, France.

Dihydrotestosterone (DHT) the physiologically most potent androgen cannot be
aromatised into oestrogen. DHT is used as a treatment for idiopathic
gynaecomastia. In order to investigate the different sites of action of DHT on
the hypothalamic-pituitary-testicular axis, two groups of adult men were studied.
Group I included 10 gonadotropin-releasing hormone (GnRH)-deficient men who were 
evaluated before and during a pulsatile infusion of GnRH alone for 2 weeks and
then in association with DHT given transdermally at doses used in the treatment
of gynaecomastia for further two weeks. Luteinizing hormone (LH) pulsatility was 
assessed at the end of each step of the study. Plasma LH levels were measured
every 15 min. Plasma testosterone (T), DHT, oestradiol (E2), free alpha-subunit
(FAS) of glycoproteic hormones and LH bioactivity were measured on pooled plasma 
samples. Group II included 12 healthy men in whom plasma T, DHT and E2 were
measured before and then 24, 48 and 72 h after the injection of 5000 IU hCG alone
or in combination with either DHT or the pure anti-androgen nilutamide. Two weeks
separated each of the 3 hCG testing. In group I, except for
bioactive/immunoreactive (B/I) LH ratio which was unchanged, GnRH treatment
induced significant rises (p < 0.01) in all plasma hormone levels, LH pulse
amplitude and frequency. During treatment with GnRH+DHT, plasma DHT levels
increased up to 16.8 +/- 2.5 nm, while plasma hormone levels, B/I LH ratio, LH
pulse amplitude and frequency were similar to those obtained with GnRH alone. In 
group II, the peak of hCG-induced T rise was not modified by either DHT or
nilutamide. In contrast, DHT reduced by 50% (p < 0.01) the E2 peak in response to
hCG. These data show that DHT exerts no direct action on the pituitary to
retroregulate LH secretion and to modify either B/I LH ratio or FAS secretion.
Its reducing effect on LH secretion is likely mediated at the hypothalamic level.
DHT does not appear to have a physiological influence on Leydig cells
steroidogenesis. Administered at therapeutic doses, DHT directly reduces
testicular aromatase activity that combined with its antigonadotropic effect
leads to the gain in the symptomatic treatment of gynaecomastia.

PMID: 17931384 [PubMed - in process]

17: Behav Brain Res. 2009 Feb 11;197(2):311-6. Epub 2008 Aug 29.

Anxiety increases the place conditioning induced by cocaine in rats.

Pelloux Y, Costentin J, Duterte-Boucher D.

Unité de Neuropsychopharmacologie Expérimentale, CNRS FRE 2735, Institut
Fédératif de Recherche Multidisciplinaire sur les Peptides, IFRMP 23, Faculté de 
Médecine et de Pharmacie de Rouen, 22, Bld Gambetta, 76183 Rouen cedex, France.

Some clinical studies have shown that anxiety disorders are often associated with
drug dependence, although it remains unclear whether these disorders are primary 
or secondary to drug abuse. We have investigated whether anxiety may be a factor 
that predisposes to cocaine use. From an outbred Wistar strain, we have selected 
male rats regarded as anxious or non-anxious on the basis of their scores on two 
behavioural tests of unconditioned anxiety, the elevated plus-maze and the
light/dark box test. They were also screened for their locomotor activity in an
inescapable novel environment and for their preference for novelty presented in a
free-choice. Rewarding effects of cocaine (2.5-20 mg/kg; i.p.) were then
determined in the conditioned place preference paradigm (CPP). Anxious and
non-anxious rats showed no difference in their responsiveness to inescapable
novelty or their preference for novelty in a free-choice procedure. Only anxious 
rats developed a CPP induced by increasing doses of cocaine, the magnitude of CPP
induced by the 10 mg/kg dose of cocaine being significantly higher than that
observed in anxious rats conditioned with saline. These results suggest that
anxiety affects the sensitivity to aversive/anxiogenic effects of cocaine. Thus, 
anxious rats which were highly responsive to positive effects of cocaine may be
more prone to develop cocaine addiction than non-anxious rats.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18793676 [PubMed - indexed for MEDLINE]

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