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Biomedical subjects

B Olivier

Publications and source records attributed to B Olivier.

At least 19 recordsLinked to original sources
PubMed1995

The anxiolytic effects of flesinoxan, a 5-HT1A receptor agonist, are not related to its neuroendocrine effects.

The effects of flesinoxan, a selective 5-HT1A receptor agonist, were studied under basal non-stress conditions and in the shock-probe burying paradigm. Flesinoxan (1 and 3 mg/kg s.c.) significantly reduced burying and freezing behaviour, indicating clear anxiolytic properties. Under non-stress conditions, injection of 3 mg/kg flesinoxan significantly enhanced plasma corticosterone and glucose levels, whereas prolactin secretion was significantly enhanced after both 1 mg/kg and 3 mg/kg flesinoxan. Flesinoxan (1 and 3 mg/kg) did not suppress shock-probe stress-induced rises in plasma corticosterone and glucose levels. The enhanced plasma prolactin levels induced by flesinoxan were not further affected by shock-probe exposure. Our data show that the anxiolytic effects of flesinoxan in the shock-probe burying paradigm are not related to increases in plasma corticosterone and glucose levels.

Animals↗
PubMed1995

The role of the medial prefrontal cortex of rats in short-term memory functioning: further support for involvement of cholinergic, rather than dopaminergic mechanisms.

The putative involvement of the dopaminergic innervation of the medial part of the prefrontal cortex (PFC) in short-term memory functioning was investigated by evaluating the effects of local infusions of dopaminergic drugs into the ventral part of the medial PFC of rats in an operant delayed-matching-to-position (DMTP) task. Two separate groups of rats were tested after bilateral microinfusion of several doses of either the dopamine receptor agonist apomorphine (APO) or the dopamine receptor antagonist cis-flupenthixol (FLU) into the ventromedial PFC. In addition, all animals were tested after infusion of several doses of the muscarinic receptor antagonist scopolamine (SCO) and the dopamine DI receptor antagonist SCH-23390 (SCH). The drugs tested affected DMTP performance differentially. APO had no effect on response accuracy, although it dose-dependently affected nose poke activity and response latencies. FLU and SCH both induced a dose-dependent, but delay-independent deterioration of response accuracy that was paralleled by increases in response latencies and decreases in nose poke frequencies, causing some animals to stop responding after infusion of the highest doses of both drugs. In contrast, SCO infusions into the ventromedial PFC induced a dose- and delay-dependent deterioration of response accuracy, that was accompanied by an increase in response latencies only. Taken together, these results provide additional support for the involvement of cholinergic, rather than dopaminergic mechanisms in short-term memory supported by the medial PFC of the rat, and they are not in favor of a functional dissociation between the dorsomedial PFC and the ventromedial PFC in the role.

Animals↗
PubMed1995

The corticosterone-enhancing effects of the 5-HT1A receptor antagonist, (S)-UH301, are not mediated by the 5-HT1A receptor.

We tried to antagonize the endocrine and behavioural changes induced by the selective 5-HT1A receptor agonist, flesinoxan, with the putative 5-HT1A receptor antagonist, (S)-UH301 ((S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin). The interaction of (S)-UH301 (3 and 10 mg/kg s.c.) with flesinoxan (3 mg/kg s.c.) showed no antagonistic effects of (S)-UH301 on flesinoxan-induced corticosterone secretion. In fact, like flesinoxan (1 and 3 mg/kg s.c.), (S)-UH301 (3 and 10 mg/kg s.c.) itself dose dependently increased plasma corticosterone levels. Unlike flesinoxan, (S)-UH301 did not induce hyperglycemia, lower lip retraction and flat body posture. Moreover, flesinoxan-induced hyperglycemia and behavioural changes were effectively antagonized by (S)-UH301, showing potent 5-HT1A receptor antagonistic effects of (S)-UH301. Therefore we conclude that (S)-UH301 is a potent 5-HT1A receptor antagonist and that the (S)-UH301-induced corticosterone secretion is mediated by a non-5-HT1A receptor mechanism.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Conditioned ultrasonic distress vocalizations in adult male rats as a behavioural paradigm for screening anti-panic drugs.

Rats may produce ultrasonic vocalizations (USV) in threatening situations. USV of adult male rats in association with aversive stimulation was evaluated as a screening method for anxiolytic drugs. The triazolobenzodiazepine alprazolam, the 5-HT uptake inhibitors fluvoxamine and clomipramine, the mixed 5-HT/NA uptake inhibitor imipramine, the full 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan, the partial 5-HT1A receptor agonists buspirone, ipsapirone and BMY 7378, the alpha 2-adrenoceptor agonist clonidine and the alpha 2-adrenoceptor antagonist yohimbine reduced conditioned USV. The classical benzodiazepines (BZD) diazepam and chlordiazepoxide were ineffective or had a very low potency to decrease USV. The partial BZD receptor agonists bretazenil, alpidem and zolpidem, the BZD receptor antagonist flumazenil, the NA uptake inhibitors desipramine and maprotiline, and the 5-HT3 receptor antagonist ondansetron had no effect on conditioned USV. The dopamine-D2 receptor antagonist haloperidol reduced USV at a very high dose. In separate experiments the effects of these drugs on locomotor activity were assessed. There was, however, no direct relationship between effects on motor behaviour and USV. In conclusion, the sensitivity of conditioned USV to 5-HT uptake inhibitors and alprazolam versus the insensitivity to classical benzodiazepines and NA uptake inhibitors provides a very interesting profile, which closely resembles the psychopharmacology of panic disorder. Also the face validity of conditioned USV towards situational panic attacks is high. We therefore propose conditioned USV in adult male rats as a novel behavioural paradigm to screen for anti-panic drugs.

Animals↗
PubMed1995

Predictive validity of the potentiated startle response as a behavioral model for anxiolytic drugs.

The fear-potentiated startle (PSR) paradigm is a putative behavioral model for the determination of anxiolytic properties of drugs. The present study further investigated the predictive validity of the model. Predictive validity is high, when only drugs clinically used as anxiolytics attenuate PSR dose dependently. Results showed that startle potentiation decreased dose dependently after the administration of the anxiolytics CDP (2.5-10 mg/kg, IP) and alprazolam (1-3 mg/kg, IP). After administration of the clinically non-anxiolytic drugs amitriptyline (2.5-10 mg/kg, IP), carbamazepine (5-20 mg/kg, IP), fentanyl (0.0025-0.04 mg/kg, SC), naloxone (2.5-10 mg/kg, IP), nicotine (0.4-1.6 mg/kg, IP), alcohol (500-2000 mg/kg, IP), and d-amphetamine (0.6-2.4 mg/kg, IP), a dose-dependent decrease in startle potentiation was not found. The PSR correctly discriminated most of the drugs tested in clinically anxiolytic and clinically non-anxiolytic drugs. However, haloperidol behaved as a false positive, and results of nicotine and alcohol were at variance with results reported by others.

Alprazolam↗
PubMed1995

Cholinergic drug effects on a delayed conditional discrimination task in the rat.

The centrally acting cholinergic antagonist scopolamine (0.025-0.10 mg/kg ip) and the peripherally acting cholinergic antagonist methyl-scopolamine (0.01-0.10 mg/kg) dose dependently impaired discriminability independent of delay in a delayed conditional discrimination task that precludes use of mediating behavior. This indicates that scopolamine does not specifically affect working memory. Drugs that enhance cholinergic transmission neither improved discriminability nor attenuated scopolamine-induced impairments. In a post hoc analysis scopolamine was found to impair discriminability in a delay-dependent manner in rats that performed at a high level in pretest sessions. Methyl-scopolamine impaired performance independently of delay in these rats. The authors suggest that a ceiling effect at short delays produced this Drug x Delay interaction of scopolamine in the best performing rats.

Animals↗
PubMed1995

[Outcome of 77 live born children with cardiac or rhythmic anomalies diagnosed in the prenatal period. Apropos of 77 cases].

Seventy-seven live born children (September 1988 to May 1993) had prenatally detected morphological cardiac malformations (61 cases) and/or arrhythmias (17 cases). The outcome of these children was analysed with an average follow-up of 21.4 months (range: 1 day to 11 years). The parameters studied were age and condition of prenatal diagnosis, the term of pregnancy, the extracardiac malformations associated and the outcome of the live born children. Fifty-two children survived with a mean follow-up of 28.2 months (range: 5 months to 11 years) and 25 children died at a mean age of 3.3 months (range: 1 day to 32 months). The cardiac malformations correlated with the postnatal diagnosis in 59 children (60 cardiac malformations). They included left or right outflow tract obstruction in 22%, septal defects or Tetralogy of Fallot with or without pulmonary atresia in 18.4%, arterial malposition in 12.9% and arrhythmias or conduction defects in 20.7% of cases. The main reason for the high mortality was the complexity of the cardiac malformations with, in particular, ventricular hypoplasia with right or left outflow tract obstruction (41% of mortality). The functional consequences of these abnormalities were only partially appreciated at prenatal diagnosis. The extracardiac malformations, more easily diagnosed, contributed less to this mortality rate. The favourable prognosis of the arrhythmias or conduction defects diagnosed prenatally was confirmed but was, however, associated with a mortality rate of 12%.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Therapeutic↗
PubMed1994

Effects of local application of dopaminergic drugs into the dorsal part of the medial prefrontal cortex of rats in a delayed matching to position task: comparison with local cholinergic blockade.

Lesions of the medial prefrontal cortex (mPFC) disrupt performance in a variety of delay tasks, which suggests that the mPFC supports short-term memory processes. The putative involvement of the dopaminergic innervation of the mPFC in these mnemonic processes was investigated by evaluating the effects of local infusions of dopaminergic drugs into the mPFC of rats in an operant delayed-matching-to-position (DMTP) task. Trained animals were provided with bilateral guide cannulae aimed at the dorsal part of the mPFC. Two separate groups of rats were tested after microinfusion of several doses of either the dopamine agonist apomorphine (APO) or the dopamine antagonist cis-flupenthixol (FLU). In addition, all animals were tested after infusion of several doses of the muscarinic antagonist scopolamine (SCO). Animals were tested 0 and 135 min after each infusion. At the 0 min interval, neither APO nor FLU affected accuracy of DMTP performance, while both drugs dose-dependently increased response latencies and decreased nosepoke frequencies. At the 135 min interval, APO had almost no effect, whereas the effects of FLU were very prominent. A number of animals no longer responded after infusion of the highest doses of FLU and those that did showed a delay-independent decrease in response accuracy. In contrast, SCO infusions into the mPFC induced a dose- and delay-dependent deterioration of DMTP performance. Taken together, these results support a direct involvement of the rat mPFC in short-term memory processes, although they implicate cholinergic rather than dopaminergic mechanisms in this function.

Animals↗
PubMed1994

Stress-induced hyperthermia in mice: hormonal correlates.

In the stress-induced hyperthermia (SIH) paradigm in group-housed male mice, the rectal temperature of last measured mice is approximately 1.5 degrees C higher than the first measured one when the temperature of each mouse is measured sequentially with an interval of 1 min. In the present study it is demonstrated that SIH is accompanied by increases in plasma ACTH, corticosterone, and glucose levels that return to baseline more or less parallel to the temperature. The simultaneous increases in temperature and plasma stress hormones strongly support the use of the SIH paradigm in mice as an animal model to study putative anti-stress or anxiolytic properties of drugs.

Adrenocorticotropic Hormone↗
PubMed1994

New animal models of anxiety.

In an attempt to develop new animal models of anxiety with face and predictive validity for the spectrum of human anxiety disorders, two new animal paradigms have been described, stress-induced hyperthermia (SIH) in mice and ultrasonic pup vocalizations (UV) in rats. In SIH mice develop enhanced body temperature in anticipation of an aversive event. This SIH can be antagonized by benzodiazepines, alcohol and 5-HT1A receptor agonists, but not by specific 5-HT reuptake inhibitors (SSRIs) or 5-HT3 receptor antagonists. When rat pups are separated from their mother and littermates they produce ultrasonic sounds, indicative of a separation distress. Benzodiazepines, 5-HT1A receptor agonists and SSRIs decrease this calling, whereas 5-HT3 receptor antagonists have no effect. Antidepressants in general do not decrease pup calling because in contrast to the SSRIs, noradrenergic uptake blockers enhance calling. These two animal models of anxiety can be added to the range of anxiety models and will be of help in predicting new putative anxiolytic drugs.

Animals↗
PubMed1994

[Surgical indications and results in 50 cases of isolated ventricular septal defects during the first year of life].

Surgical indications of isolated ventricular septal defects (VSD) with large shunts are a common problem in paediatric cardiology. The present study was undertaken retrospectively and continuously over 5 years in 50 patients in whom the age of diagnosis varied from birth to 1 year. The surgical results are presented and the clinical and paraclinical parameters used for determining the surgical indications are reviewed. Only 16 out of 50 children (32%) were operated without catheter study. However, since February 1992, when colour Doppler echocardiography became a routine investigation in the department, 75% of children have been operated on echocardiographic data alone. Knowing that the risk of pulmonary vascular disease is practically nil in this condition at this age, the most important problem lies in distinguishing between single and multiple VSDs. Until recently, angiography has always been the reference investigation. In this series, it did not appear to be superior to a good colour Doppler study. The surgical results showed a hospital mortality of 4%, the persistence of a well tolerated VSD in 16% of cases, none of which required reoperation. Two cases of complete atrioventricular block required permanent cardiac pacing. The authors conclude that when echocardiography provides all the necessary data concerning site, number, size and haemodynamic consequences of VSD, catheterisation may be dispensed with at this age. The surgical indication is, generally, closure of the VSD by a patch, usually possible by a right atrial approach; pulmonary artery banding is an exceptional necessity in infants with a precarious haemodynamic status and/or with multiple apical VSD.

Angiocardiography↗
PubMed1993

Classification of psychotropic drugs based on pharmaco-electrocorticographic studies in vigilance-controlled rats.

The effects of a number of psycho-active drugs on electrocorticographic activity (ECoG) of the rat have been studied. Frontoparietal ECoG was recorded during 6-min periods immediately before drug/vehicle administration and starting at 20 and 45 min after administration. For each 6-min recording time, a mean power spectrum was calculated and smoothed. A quotient of the power at 20 and 45 min after and before drug, respectively, was then calculated. These quotients were used as input for an analysis of variance, followed by a t test and a normalization for the degrees of freedom, resulting in so-called n-profiles. Although each drug has its own characteristic n-profile, n-profiles of drugs belonging to the same clinical class have some characteristics in common. An automated classification system of psychotropic drugs, based on parameters extracted from n-profiles by discriminant analysis, is presented. For the antidepressant drug class the success rate of correct classification of antidepressant drugs is between 53 and 88%, for a neuroleptic drug in the neuroleptic drug class the success rate is 87%, for an anxiolytic drug in the anxiolytic drug class 100% and for a psychostimulant drug in the psychostimulant drug class between 86 and 100%. For a reliable classification of a drug about 10 n-profiles of active doses are needed. Using n-profiles, it appeared also possible to discriminate between antidepressant, neuroleptic, anxiolytic and psychostimulant drugs based on visual judgement. Moreover, visual evaluation of the n-profiles enables 4 subclasses to be recognized within the antidepressant class, 2 subclasses within the neuroleptic and 2 subclasses within the anxiolytic class.

Animals↗
PubMed1992

The effects of intraventricular administration of eltoprazine, 1-(3-trifluoromethylphenyl)piperazine hydrochloride and 8-hydroxy-2-(di-n-propylamino)tetralin on resident intruder aggression in the rat.

Various serotonergic agents may reduce aggression in rats, but how they act in different parts of the brain is unknown. This study attempted to unravel part of this question by application of different serotonergic ligands into the lateral ventricle (i.c.v.) of male rats (resident-intruder aggression). 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin; 1 and 10 micrograms), a specific 5-HT1A agonist, affected neither aggression nor any other behaviour. The mixed 5-HT1A,B,C agonist, TFMPP (1-(3-trifluoromethylphenyl)piperazine hydrochloride), and the 5-HT1A/1B agonist, eltoprazine ((1-(2,3)-dihydro-1,4-benzodioxin-5-yl)piperazine hydrochloride), suppressed aggression at i.c.v. doses of 10 and 30 micrograms. This reduction was not caused by sedation. These data suggest a role of postsynaptic 5-HT1B receptors in mediating the anti-aggressive effects of mixed 5-HT1 agonists.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Flesinoxan shows antidepressant activity in a DRL 72-s screen.

Schedules which selectively reinforce low rates of responding (DRL, differential reinforcement of low rate) distinguish between antidepressants and other types of drugs. In a DRL schedule a subject is required to pause for a specified minimum period of time between two consecutive responses in order to obtain a reinforcer. The dependent variables are rate of responding and rate of reinforcement. Response patterns of rats treated with clinically effective antidepressant drugs such as imipramine (2.0-32.0 mg/kg) or fluvoxamine (4.0-32.0 mg/kg) are characterized by a decrease in response rate and an increase in reinforcement rate. Treatment with the 5-HT1A agonist flesinoxan (0.1-3.0 mg/kg) also dose-dependently decreased response rates while at the same time increasing reinforcement rates. Chlordiazepoxide (2.5-20.0 mg/kg) and diazepam (0.25-2.0 mg/kg) had no effects in the present experiment. d-Amphetamine increased response rates at low doses (0.5-2.0 mg/kg), and decreased it at the higher doses (4.0 mg/kg), but reinforcement rates were unaltered. Overall analysis of the effects of haloperidol (0.02-0.32 mg/kg) showed decreased responding and increased reinforcement rates. Post hoc analysis, however, clearly differentiated between haloperidol's profile and that of the antidepressants. As such, the results of the present experiment show that flesinoxan might possess antidepressant activity in humans.

Animals↗
PubMed1992

Effects of anxiolytic and antidepressant drugs on long-lasting behavioural deficits resulting from one short stress experience in male rats.

Exposure of male Wistar rats to one single session of ten inescapable footshocks induces changes in the behavioural responses to environmental stimuli as measured in the "noise test" 14 days later. Shocked (S) rats showed decreased locomotion and rearing during the first 3 min of exposure to a novel environment compared to control (C) rats. When the 85 dB background noise was switched off a marked immobility response emerged in S rats, concomitant with a further decrease in locomotion and rearing. In response to noise off, C rats showed hardly any immobility and a much smaller reduction in locomotion and rearing compared to S rats. These long-lasting changes in behaviour were not reversed by acute treatment with the antidepressants fluvoxamine (3.0-30.0 mg/kg) and desmethylimipramine (DMI, 2.5-10.0 mg/kg) injected IP 30 min before the noise test on day 14 following the shock session. Chronic treatment (day 1 to day 14) with fluvoxamine or DMI did not reverse the behavioural deficits induced by shock exposure. Diazepam (0.6-5.0 mg/kg) administered acutely only reversed the effects of shock on locomotion during the first 3 min of the noise test. Chronic treatment with diazepam normalized the shock-induced decrease in locomotion and attenuated the rearing decrease during the first 3 min of the test, and partially restored shock-induced changes in behavioural response to switching off the noise. The most potent drug in this study was the 5-HT1A receptor agonist flesinoxan (0.3-3.0 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Assessment of the stimulus properties of anxiolytic drugs by means of the conditioned taste aversion procedure.

The conditioned taste aversion (CTA) procedure has recently been described as a more rapid alternative to two-lever operant procedures in drug discrimination research. We trained different groups of rats to discriminate the benzodiazepine chlordiazepoxide (CDP, 20 mg/kg) or the 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.4 mg/kg) from saline by means of the CTA procedure. The results were in agreement with findings from two-lever operant drug discrimination procedures. However, discrimination training took 40 sessions in the case of CDP and 72 sessions for 8-OH-DPAT, which is comparable to results obtained with two-lever operant procedures. Dose-response curves were determined and generalization tests were performed for different benzodiazepine and nonbenzodiazepine anxiolytics. Baseline behavior deteriorated in the course of generalization and substitution testing, thus preventing further generalization testing. Our experience is that the use of the CTA procedure in drug discrimination research does not have sufficient advantages over traditionally used procedures to replace the latter.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Rodent models of aggressive behavior and serotonergic drugs.

Various models of rodent agonistic behaviour are described, which differentiate between offensive and defensive/flight models. Particular attention is given to one male and one female paradigm for offensive aggression, viz. resident-intruder or territorial (RI) and maternal aggression (MA). After an overview of the serotonin (5-HT) system in the CNS, a description is given of the ligands available. Subsequently the effects of various drugs affecting serotonergic transmission in the RI- and MA-paradigms are described. The 5-HT1A agonists buspirone, ipsapirone and 8-OH-DPAT decreased aggression in RI and MA, but simultaneously led to a marked decrease in social interest and activity, indicative of a non-specific anti-aggressive profile. Non-selective 5-HT1 agonists, such as RU 24969, eltoprazine (DU 28853), and TFMPP reduced aggression quite specific and did not decrease social interest or exploration, but sometimes even increased these behaviours. In RI and MA the behavioural effects of these drugs were roughly similar. In contrast, MA was more sensitive to the treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression only non-specifically at the highest dose. DOI, a 5-HT2 and 5-HT1C agonist, decreased aggressive behaviour and increased inactivity, without affecting social interest and exploration in RI as well as MA. This was, however, accompanied by 'wet dog shaking', characteristic of 5-HT2-receptor stimulation. The non-specific 5-HT agonist (and 5-HT3 antagonist) quipazine also induced 'wet dog shaking' at doses which suppressed aggression, social interest and exploration but increased inactive behaviours (sitting and lying). The discussion attempts to delineate a role for 5-HT receptor subtype involvement in the modulation of aggression, with the restrictions we clearly face with regard to the lack of specific serotonergic agonists and antagonists for certain receptor subtypes. By and large, male and female rats react similarly to treatment with serotonergic drugs stressing the consistent role of 5-HT in different forms of aggression.

Aggression↗