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Biomedical subjects

Berend Olivier

Publications and source records attributed to Berend Olivier.

At least 19 recordsLinked to original sources
PubMed2007

Delay aversion: effects of 7-OH-DPAT, 5-HT1A/1B-receptor stimulation and D-cycloserine.

Impulsive individuals often display an aversion to waiting for rewards. Delay aversion can be quantified in rats in a delayed reward task, in which animals choose between an immediately available, small reward, and a large reward available after a delay. In previous research conducted at our laboratory and in literature, positive correlations between delay aversion and aggression, substance abuse and persistence during extinction of conditioned responses were found. The correlations suggest a possible shared pharmacology. Therefore, we tested drugs with known effects on these behaviors for possible effects on delay aversion: the dopamine D(3)-receptor agonist 7-OH-DPAT, the 5-HT(1A)-receptor agonist flesinoxan, the 5HT(1A/1B)-receptor agonist eltoprazine, and the NMDA-receptor agonist d-cycloserine. The results show that 7-OH-DPAT slightly decreased choice for the large reward. Flesinoxan disrupted task execution by lowering choice for the large reward even at a delay of 0 s. Eltoprazine slightly increased choice for the large reward, but the 5-HT(1B)-antagonist GR127935 had no effect. Administration of D-cycloserine also had no effect on choice behavior. The data suggest the dopamine D(3)-receptor and the 5-HT(1B)-receptor are interesting targets for treating delay aversion impulsivity. These targets were correctly predicted by the positive correlation between delay aversion and aggressive behavior and the intimate links between delay aversion and substance abuse disorders.

Animals↗
PubMed2006

A new animal welfare concept based on allostasis.

Animal welfare is an increasing issue of public concern and debate. As a result, many countries are reconsidering the way animal welfare is embedded in the legislation and rules for housing and care of animals. This requires general agreement of what animal welfare is. Unfortunately, the current science of animal welfare is less scientific than what has been claimed. In our view, it is overly guided by anthropocentric thinking about how animals ought to be handled and neglects the latest concept of physiology: 'The Allostasis Concept'. Allostasis, which means stability through change, has the potential to replace homeostasis as the core model of physiological regulation. Not constancy or freedoms, but capacity to change is crucial to good physical and mental health and good animal welfare. Therefore, not homeostasis but allostasis is at the basis of our new animal welfare concept. This paper is aimed at a broader scientific discussion of animal welfare that includes knowledge from the latest scientific developments in neurobiology and behavioral physiology, and generates views that are extremely relevant for the animal welfare discussion.

Allostasis↗
PubMed2006

Long-term behavioral changes after cessation of chronic antidepressant treatment in olfactory bulbectomized rats.

BACKGROUND: Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical central nervous system changes, reminiscent of symptoms of human depression. Moreover, depression-like behavior after OBX can be reversed with antidepressant drugs. However, the lasting effects of these antidepressant drugs on behavior after cessation of treatment have never been studied. METHODS: Male rats received OBX or sham surgery. After recovery, animals received 14 consecutive daily doses of imipramine (20 mg/kg), escitalopram (5 and 10 mg/kg), or vehicle. Animals were tested in an open field after acute, sub-chronic, and chronic injections, as well as 1, 2, 6, and 10 weeks after cessation of treatment. RESULTS: The OBX-induced hyperactivity was normalized after sub-chronic administration of imipramine and escitalopram. Two weeks after treatment, activity of OBX animals was comparable to sham-treated animals, but after 6 weeks, OBX animals treated with both doses of escitalopram had returned to pre-treatment hyperactivity levels. The OBX animals treated with the high imipramine dose (20 mg/kg) retained activity levels comparable to sham-treated animals until 10 weeks after cessation of treatment. CONCLUSIONS: Chronic but not acute administration of imipramine and escitalopram normalizes OBX-induced hyperactivity. This effect continues for up to 10 weeks after cessation of treatment in a dose dependant manner.

Analysis of Variance↗
PubMed2006

Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning.

There is accumulating evidence that AKT signaling plays a role in the pathogenesis of schizophrenia. We asked whether Akt1 deficiency in mice results in structural and functional abnormalities in prefrontal cortex (PFC). Exploratory transcriptional profiling revealed concerted alterations in the expression of PFC genes controlling synaptic function, neuronal development, myelination, and actin polymerization, and follow-up ultrastructural analysis identified consistent changes in the dendritic architecture of pyramidal neurons. Behavioral analysis indicated that Akt1-mutant mice have normal acquisition of a PFC-dependent cognitive task but abnormal working memory retention under neurochemical challenge of three distinct neurotransmitter systems. Thus, Akt1 deficiency creates a context permissive for gene-gene and gene-environment interactions that modulate PFC functioning and contribute to the disease risk associated with this locus, the severity of the clinical syndrome, or both.

Animals↗
PubMed2006

Relationship of delay aversion and response inhibition to extinction learning, aggression, and sexual behaviour.

Impulsivity is an important symptom of many psychiatric disorders, and can be divided into two subtypes: response inhibition deficits and delay aversion. In the present study, we investigated the relationship between delay aversion and response inhibition, both to each other and to locomotion, extinction of conditioned responses, sexual behaviour, and aggressive behaviour. To that end, we quantified the behaviour of 24 rats in several tests. To measure response inhibition, rats were trained in a stop-signal task. In this operant task, rats were rewarded food if they inhibited execution of a response after presentation of an audible stop-signal. Delay aversion was measured in an operant task in which rats made a choice between a small, immediately available reward and a large reward available after a delay. The results showed that delay aversion and response inhibition were independent. Responses during extinction and various measures of aggressive behaviour were positively correlated to delay aversion. The speed of go-trials in the stop-task was correlated to non-aggressive behaviour. We conclude that the role of response inhibition in various behaviours is small, but delay aversion in particular contributes to several other behaviours, such as aggressive behaviour and extinction.

Aggression↗
PubMed2006

Effects of genetic background and null mutation of 5-HT1A receptors on basal and stress-induced body temperature: modulation by serotonergic and GABAA-ergic drugs.

The stress-induced hyperthermia procedure, in which effects of drugs on basal (T(1)) and stress-induced body temperature (T(2)) are measured, predicts anxiolytic drug effect. Serotonergic drugs alter these responses and here, we studied the role of 5-HT(1A) receptors in stress-induced hyperthermia by using 5-HT(1A) receptor knockout mice. Three strains (129/Sv, Swiss Webster and C57Bl6) were used because genetic background can significantly modulate the null phenotype. We found that GABA-ergic drugs with an anxiolytic profile and stimulate alpha(2) subunit containing GABA(A) receptors, including diazepam and L838,417, result in reduced DeltaT (DeltaT=T(2)-T(1)). The alpha(1) subunit containing GABA(A) receptor was found to be primarily involved in regulation of basal body temperature T(1) and its stimulation can induce hypothermia. In addition, stimulation of 5-HT(1A) receptors by buspirone results in a reduced DeltaT, while stimulation of 5-HT(7) receptors primarily results in hypothermia. The null mutation of 5-HT(1A) receptors resulted in differences in drug-sensitivity that was further modulated by the genetic background. In particular, the null mutation on the SW and C57Bl6 backgrounds resulted in differential diazepam/L838,417 and 5-CT responses respectively. This indicates an interaction between the 5-HT(1A) receptor and genetic background and demonstrates the importance of selecting the background strain in a receptor knockout model.

Animals↗
PubMed2006

The stress-induced hyperthermia paradigm as a physiological animal model for anxiety: a review of pharmacological and genetic studies in the mouse.

This paper reviews the function, brain mechanisms and pharmacology of stress-induced hyperthermia (SIH) in a broad context. Hyperthermia itself is induced by all stressful stimuli and can be found across numerous species, including humans. As a model for anxiety, the process of insertion of a rectal probe increases temperature ranging from about 0.5-1.5 degrees C in 10-15min is called SIH. This temperature increase can be blocked by anxiolytic drugs. The methodological as well as pharmacological aspects of the group- (G-SIH) and singly housed (SIH) version of the paradigm are described in detail. Also, an overview is presented about studies using the SIH procedure in genetically modified mice together with the potential interference with immunological induction of a febrile response. The paper also presents data that highlight some of the limitations of the SIH procedure for use of drugs like nicotine, which contain particular characteristics such as short in vivo half-life, and/or disturbance of thermoregulation. The advantages and disadvantages of the SIH procedure as a physiological model of anxiety are discussed.

Animals↗
PubMed2006

Behavioral effects of modafinil in marmoset monkeys.

RATIONALE: Modafinil is increasingly used in sleep disturbances in general and in neurodegenerative diseases and is recently being used in healthy people for attention control. However, the application of modafinil is possibly not only restricted to alertness enhancing effects. More insight in this compound may lead to new applications. Not all behavioral aspects have been studied sufficiently; therefore, more detailed investigations on modafinil's positive and aversive behavioral effects are addressed in this paper. OBJECTIVES: Determination of effects of modafinil in marmoset monkeys with observational methods and with behavioral tests measuring locomotor activity, hand-eye coordination, response to a threat situation and startle response. MATERIALS AND METHODS: Two hours after oral administration of modafinil in doses of 50, 100, 150, and 225 mg/kg, animals were observed and tested in the behavioral test systems. RESULTS: Locomotor activity was increased after 100 mg/kg modafinil in the Bungalow test and after 100, 150, and 225 mg/kg, as found in the movement parameters of the human threat test. Moreover, modafinil showed anxiolytic-like effects in the human threat test. No other side effects were observed, nor were the hand-eye coordination and startle response affected. CONCLUSIONS: Besides psychostimulation, modafinil has no aversive effects in the doses used in the domains measured. The potential anxiolytic-like effects of modafinil may create new possibilities for the therapeutic use of modafinil.

Acoustic Stimulation↗
PubMed2006

Serotonin and the neurobiology of the ejaculatory threshold.

Disorders of the ejaculatory threshold, such as lifelong premature ejaculation, are fairly common in humans and can have a great impact on the quality of life. Research in humans and rats have indicated that increased serotonin levels in the central nervous system elevate the ejaculatory threshold, probably via 5-HT(1B) and 5-HT(2C) receptors, whereas depletion of serotonin decreases the ejaculatory threshold. 5-HT(1A) receptor activation strongly lowers the ejaculatory threshold, probably mediated by both the reduction of serotonin levels via presynaptic 5-HT(1A) receptors and yet unknown effects of postsynaptic 5-HT(1A) receptors. The present review attempts to integrate psychopharmacological data on serotonergic control over ejaculation with the knowledge of the neuroanatomical substrate of ejaculation, indicating the importance of the lumbosacral spinal cord, the nucleus paragigantocellularis, the lateral hypothalamic area and several other supraspinal areas. In addition, the gaps in our understanding of the role of serotonin in the ejaculatory threshold are discussed. Filling in those gaps might help to design specific drugs that alter the ejaculatory threshold, thereby alleviating ejaculatory disorders.

Animals↗
PubMed2006

Spontaneously hypertensive rats do not predict symptoms of attention-deficit hyperactivity disorder.

The validity of the Spontaneously Hypertensive rat (SHR) as a model for Attention Deficit Hyperactivity Disorder (ADHD) is explored by comparing the SHR with Wistar-Kyoto (WKY) and Wistar rats in a number of different tests. In the open field, SHR are hyperactive compared to both Wistar and WKY, but only at specific ages. At those ages, methylphenidate (1mg/kg) did not attenuate hyperactivity. Subsequently, a dose response study of methylphenidate (0.1-10mg/kg) was conducted in the Differential Reinforcement of Low-rate responding (DRL)-72s and five-choice serial reaction time tests (5-CSRTT). Compared to WKY but not Wistar rats, SHR performed worse on the DRL-72s. Performance was not improved by methylphenidate (0.1-1.0mg/kg). In the 5-CSRTT, attentional performance was similar for all rat strains, but Wistar rats made more impulsive responses than both the SHR and the WKY. Methylphenidate only attenuated impulsivity in Wistar rats. Because SHR do not consistently display symptoms of ADHD across the different tests, and methylphenidate effects were observed in both WKY and Wistar rats, but not in SHR, we conclude that SHR is not a representative animal model for ADHD.

Age Factors↗
PubMed2006

Distribution and expression of CRF receptor 1 and 2 mRNAs in the CRF over-expressing mouse brain.

Corticotropin-releasing factor (CRF) acts through CRF 1 and CRF 2 receptors (CRF1, CRF2). To test the hypothesis that CRF controls the expression of these receptors in a brain site- and receptor-type specific manner, we studied CRF1 mRNA and CRF2 mRNA expressions in mice with central CRF over-expression (CRF-OE) and using in situ hybridization. CRF1 and CRF2 mRNAs appear to be differentially distributed across the brain. The brain structures expressing the receptors are the same in wild-type (WT) and in CRF-OE mice. We therefore conclude that chronically elevated CRF does not induce or inhibit expression of these receptors in structures that normally do not or do, respectively, show these receptors. However, from counting cell body profiles positive for CRF1 and CRF2 mRNAs, clear differences appear in receptor expression between CRF-OE and WT mice, in a brain-structure-specific fashion. Whereas some structures do not differ, CRF-OE mice exhibit remarkably lower numbers of CRF1 mRNA-positive profiles in the subthalamic nucleus (-38.6%), globus pallidus (-31.5%), dorsal part of the lateral septum (-23.5%), substantia nigra (-22,8%), primary somatosensory cortex (-18.9%) and principal sensory nucleus V (-18.4%). Furthermore, a higher number of CRF2 mRNA-positive profiles are observed in the dorsal raphe nucleus (+32.2%). These data strongly indicate that central CRF over-expression in the mouse brain is associated with down-regulation of CRF1 mRNA and up-regulation of CRF2 mRNA in a brain-structure-specific way. On the basis of these results and the fact that CRF-OE mice reveal a number of physiological and autonomic symptoms that may be related to chronic stress, we suggest that CRF1 in the basal nuclei may be involved in disturbed information processing and that CRF2 in the dorsal raphe nucleus may play a role in mediating stress-induced release of serotonin by CRF.

Animals↗
PubMed2006

Acute and subchronic effects of amitriptyline 25mg on actual driving in chronic neuropathic pain patients.

The acute and subchronic effects of low doses nocturnally administered amitriptyline were compared to placebo in a double-blind crossover randomized study on driving ability and driving-related skills involving seven chronic neuropathic pain patients. Performance testing occurred at the first and last day of each 15-day drug administration period, which was preceded by a 6-day washout phase. A standardized method of measuring driving ability, the on-the-road driving test, was performed on all visits. Patients were instructed to drive with a steady lateral position while maintaining a constant speed of 95 km/h. The primary outcome of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), which is an index of weaving of the car. At the first treatment day, driving performance was significantly impaired in patients after nocturnal administration of 25 mg amitriptyline compared to placebo. The increase in SDLP of 3 cm was higher than the increment generally observed with a blood alcohol concentration of 0.5 mg/ml or higher, the legal limit for driving in many countries. Also, reaction times on a memory test were significantly increased, indicating worse performance after acute treatment of amitriptyline compared to placebo. In contrast, after 2 weeks of treatment, no significant differences were found between amitriptyline and placebo, suggesting that tolerance had developed to the impairing effects of amitriptyline.

Adult↗
PubMed2006

Pain and attention: attentional disruption or distraction?

UNLABELLED: The effect of pain processing on attention capacity during visual search was examined in 2 experiments. In the first experiment, we investigated whether pain draws on the same limited resources as attentional task performance. It was hypothesized that pain would negatively affect task performance under different load manipulations. Low and high load conditions of a visual search task were presented in a mixed design combined with a painfully cold or neutral cold pressor test. Performance was not affected by pain. In experiment 2, low and high load conditions were separated in different blocks to study whether pain perception was affected when task load could be anticipated. Again, pain did not significantly affect task performance. In contrast, subjective pain intensity scores were significantly lower after performing the high load compared with the low load condition. Simultaneous recordings of event-related potentials indicated an increased negativity during the pain compared with the control condition. Also, in the early (350 to 450 msec) interval of event-related potentials, an increase in negativity was found for the high load compared with the low load condition. Topographic distributions suggested that pain and task load are mediated by qualitatively different resources. PERSPECTIVE: Our findings indicate that highly demanding attentional task performance and pain processing interfere as a result of difficulties in allocating attention. The clinical relevance of this finding is that performing a highly demanding task might distract attention from pain.

Adult↗
PubMed2006

Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects.

The vigilance-enhancing agent modafinil has neuroprotective properties: it prevents striatal ischemic injury, nigrostriatal pathway deterioration after partial transsection and intoxication with 1-methyl-1,2,3,6-tetrahydropyridine. The present study determines the protective effects of modafinil in the marmoset 1-methyl-1,2,3,6-tetrahydropyridine Parkinson model on behavior and on monoamine levels. Twelve marmoset monkeys were treated with a total dose of 6 mg/kg 1-methyl-1,2,3,6-tetrahydropyridine. Simultaneously, six animals received a daily oral dose of modafinil (100 mg/kg) and six animals received vehicle for 27 days. Behavior was observed daily and the locomotor activity, hand-eye coordination, small fast movements, anxiety-related behavior and startle response of the animals were tested twice a week for 3 weeks. Modafinil largely prevented the 1-methyl-1,2,3,6-tetrahydropyridine-induced change in observed behavior, locomotor activity, hand-eye coordination and small fast movements, whereas the vehicle could not prevent the devastating effects of 1-methyl-1,2,3,6-tetrahydropyridine. Dopamine levels in the striatum of the vehicle+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 5% of control levels, whereas the dopamine levels of the modafinil+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 41% of control levels. The present data suggest that modafinil prevents decrease of movement-related behavior and dopamine levels after 1-methyl-1,2,3,6-tetrahydropyridine intoxication and can be an efficaceous pharmacological intervention in the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Pharmacotherapy for the treatment of aggressive behavior in general adult psychiatry: A systematic review.

OBJECTIVE: To systematically review the evidence for pharmacologic management of outwardly directed aggressive behavior in general adult psychiatry. DATA SOURCES: Literature searches in PubMed, EMBASE, PsycINFO, and Cochrane libraries from 1966 through March 2005 were used to identify relevant studies. The keywords aggression, violence, anger, and hostility combined with drug therapy, psychotropic drugs, adrenergic beta-antagonists, anticonvulsants, anti-depressants, antipsychotic agents, benzodiazepines, and lithium were searched. Furthermore, the retrieved publications were searched for additional references. STUDY SELECTION: All randomized controlled trials addressing pharmacotherapy for aggression or aggression-related symptoms were included, except studies addressing the "emergency situation" and studies conducted in specialized psychiatric or non-psychiatric settings. DATA EXTRACTION: Evidence synthesis was performed using the "best-evidence principle." Two authors independently adjudicated methodological quality and generalizability to daily clinical practice. DATA SYNTHESIS: Thirty-five randomized controlled trials met the inclusion criteria and were evaluated. On the basis of a best-evidence synthesis model, weak evidence for antiaggressive effects of antipsychotics, anti-depressants, anticonvulsants, and beta-adrenergic-blocking drugs was found. Atypical antipsychotics appeared superior to typical antipsychotics. The use of various outcome measures and insufficient data reporting in the individual studies hampered the quantitative assessment of efficacy across studies. Further limitations of the available randomized controlled trials included small sample sizes, short study duration, and poor generalizability to daily clinical practice setting. CONCLUSIONS: Whereas pharmacotherapy is frequently applied in aggressive patients, only weak evidence of efficacy of various drug classes was found. Consensus about the use of aggression measurement scales in clinical trials is necessary for future research. Furthermore, large-scale trials with more naturalistic designs, as opposed to classical randomized controlled trials with strict inclusion and exclusion criteria, may be advisable in order to obtain results that are more generalizable to daily clinical practice.

Adolescent↗
PubMed2005

5-HT1B receptors and aggression: a review.

The serotonergic (5-HT) system in the brain is involved in the modulation of offensive aggressive behavior. The dogma that activity of the 5-HT system is inversely related to aggression is obsolete now. Research on the status of the 5-HT system before, during and after the execution of aggression is ongoing but has not yet led to a clear picture about the actual functional role of the 5-HT system, the more because state versus trait aggression seems to play a pivotal role in the outcome. Pharmacological challenges pinpoint 5-HT(1A) and 5-HT(1B) receptors as key players in the modulation of offensive aggression. This review emphasizes in particular the role of postsynaptic 5-HT(1B) (hetero) receptors as a premier site to modulate offensive aggression. Modulation of the firing and 5-HT release of the serotonergic neuron, via presynaptic 5-HT(1A) (auto) receptors, presynaptic 5-HT(1B) (auto) receptors and serotonergic transporters, may also have striking influences on aggression under certain conditions. Therefore, it is hypothesized that postsynaptic 5-HT(1B) (hetero) receptors directly influence the executive, consummatory phases of agonistic behavior, whereas presynaptic serotonergic feedback systems are particularly useful in the introductory (appetitive) phases of the agonistic behavioral complex.

Aggression↗
PubMed2005

Do similar neural systems subserve aggressive and sexual behaviour in male rats? Insights from c-Fos and pharmacological studies.

It is a common belief that male aggressive and sexual behaviour share many of the underlying neurobiological, neurological, pharmacological and neuroendocrine mechanisms. Therefore, we studied brain activation patterns in male rat after performance of aggressive and sexual behaviour and compared serotonergic pharmacology in the same paradigms to delineate possible similarities and differences. Patterns of Fos-immunoreactivity induced by aggressive and sexual encounters of Wild-type male Brown Norway rats were studied to localise the commonly activated (functionally shared) parts of the circuitry, and the specific (functionally different) parts of the neuronal circuitry. Some brain areas (caudal medial preoptic area and medial amygdala) were commonly activated, but other areas (e.g. posterodorsal parts of the medial amygdala, rostral preoptic and premammillary hypothalamus) showed remarkably specific differences in neural activation. 5-HT(1A) receptor agonists inhibit aggressive, but stimulate male sexual behaviour, whereas 5-HT(1B) receptor agonists inhibit both types of behaviour. Selective serotonin reuptake inhibitors share comparable inhibitory effects in aggression and sexual behaviour, although only at relatively high doses. We propose that separate hard-wired neural systems exist in the brain for aggressive and sexual behaviours, modulated via hierarchically 'higher-level' brain areas that are involved in the integration (gating) of the behavioural outcome of an organism.

Aggression↗