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ABSTRACT: Agressie wordt tegenwoordig omschreven als de bewuste intentie om anderen pijn, vernedering of schade te berokkenen, terwijl
dit door hen ook als zodanig wordt ervaren. Deze definitie is echter geenszins sluitend voor humane agressie omdat in de mens,
meer dan bij welke andere diersoort ook, agressie extreem variabel is. Voorbeelden hiervan zijn openlijke aanval, verbale
agressie, plagen, gewelddadige gedachten, wraakzuchtige dromen, zelfmoord, et cetera.
04/2012; 4(1):1-6.
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ABSTRACT: Lang is gedacht dat het volwassen zenuwstelsel van de mens en andere zoogdieren stabiel is. Na de vroege embryonale aanleg
en verdere ontwikkeling na de geboorte zouden geen nieuwe zenuwcellen meer worden gevormd. Omdat de structuur van onze hersenen
gedurende ons gehele volwassen leeftijd niet wijzigt en er pas veranderingen optreden door celdood op latere leeftijd (door
zowel normale veroudering als door ziekten zoals de ziekte van Parkinson of Alzheimer) is het niet verwonderlijk dat deze
opvatting vanaf het midden van de negentiende eeuw een dogma in de neurowetenschappen is geweest. Pas recentelijk werd duidelijk
dat het brein helemaal niet zo onveranderlijk is maar juist erg plastisch, waardoor het op allerlei externe factoren, ook
op hoge leeftijd, adequaat kan reageren. Deze plasticiteit komt met name tot uiting als een verandering in het aantal contacten
tussen cellen (synapsen). Daarnaast zijn er recente aanwijzingen dat bepaalde zenuwcellen nog in staat zijn te delen, een
proces dat neurogenese wordt genoemd. Ook blijkt dat dit proces van neurogenese betrokken is bij zowel normale hersenprocessen,
zoals leren en geheugen, maar ook bij het optreden van psychiatrische ziekten zoals depressie of posttraumatische stressstoornis
(ptsd).
04/2012; 6(3):59-62.
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ABSTRACT: Serotonin plays a key role in sexual behavior. In serotonin transporter (SERT) knockout rats (-/-), basal extracellular 5-HT levels are considerably increased, indicating a serotonergic disturbance. Heterozygous SERT(+/-) rats express 50% of SERT in comparison to wild-type rats and may therefore model the s/s phenotype of the human SERT promoter (5-HTTLPR) polymorphism.
In the present study, we used both homozygote and heterozygote SERT knockout and wild-type rats (+/+) to study the putative role of the SERT in female sexual behavior.
Female rats were brought into estrous by hormonal injections before a paced mating sex test. The effects of the 5-HT(1A)/5-HT(7) receptor agonist (+/-)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (+/-8-OH-DPAT) (0.03-1 mg/kg s.c.) and the 5-HT(1A) receptor antagonist WAY-100635 (0.1-1-mg/kg i.p.) on sexual behaviors of the females were tested separately and in a selected combination of both in all three genotypes.
Proceptive (darting and hopping) and receptive (lordosis) behaviors were quantified.
Basal proceptive and receptive sexual activities were not different between SERT+/+, +/- and -/- female rats. The dose-effect curve after +/-8-OH-DPAT for these activities was clearly shifted to the right in SERT-/- animals compared to other genotypes. WAY-100635 alone had no effect on sexual behavior in any genotype, but was able to antagonize the +/-8-OH-DPAT-induced decrease in sexual activities indicating the involvement of the 5-HT(1A) receptor.
The absence (-/-) or reduced (+/-) expression of SERT does not affect basal sexual activity in female rats in a paced mating situation. The data indicate a desensitized 5-HT1A receptor in the SERT-/-, but not in the SERT+/- females. Under normal basal conditions, desensitized 5-HT1A receptors apparently do not play a role in female sexual behavior of the SERT-/-. However, upon activation of the 5-HT1A receptor in "normal" females (SERT+/+ and SERT+/-), a hyposexual behavior is induced.
Journal of Sexual Medicine 04/2010; 7(7):2424-34. · 3.55 Impact Factor
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ABSTRACT: In anxiety research, the search for models with sufficient clinical predictive validity to support the translation of animal studies on anxiolytic drugs to clinical research is often challenging. This review describes the stress-induced hyperthermia (SIH) paradigm, a model that studies the activation of the autonomic nervous system in response to stress by measuring body temperature. The reproducible and robust SIH response, combined with ease of testing, make the SIH paradigm very suitable for drug screening. We will review the current knowledge on the neurobiology of the SIH response, discuss the role of GABA(A) and serotonin (5-HT) pharmacology, as well as how the SIH response relates to infectious fever. Furthermore, we will present novel data on the SIH response variance across different mice and their sensitivity to anxiolytic drugs. The SIH response is an autonomic stress response that can be successfully studied at the level of its physiology, pharmacology, neurobiology and genetics and possesses excellent animal-to-human translational properties.
European Journal of Pharmacology 06/2008; 585(2-3):407-25. · 2.52 Impact Factor
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ABSTRACT: 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.
Behavioural Brain Research 12/2006; 175(1):75-81. · 3.42 Impact Factor
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ABSTRACT: 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.
European Journal of Pharmacology 12/2006; 550(1-3):84-90. · 2.52 Impact Factor
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Berend Olivier,
Theo Zethof,
Tommy Pattij,
Meg van Boogaert,
Ruud van Oorschot,
Christina Leahy, Ronald Oosting,
Arjan Bouwknecht,
Jan Veening,
Jan van der Gugten,
Lucianne Groenink
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ABSTRACT: When mammals, including man, are confronted with a stressful event, their core body temperature rises, stress-induced hyperthermia. In mice, the stress-induced hyperthermia procedure has been developed to measure antistress or anxiolytic-like effects of psychoactive drugs. Group-housed and singly housed versions of the stress-induced hyperthermia generate comparable results. Because the number of animals needed to perform an experiment is much lower in the singly housed versus the group-housed procedure, the former is the test of choice for pharmacological testing. A typical stress-induced hyperthermia test starts with an injection 60 min before the first rectal temperature measurement (T(1)), followed by a second temperature measurement (T(2)) 10-15 min later. The difference DeltaT (=T(2)-T(1)) is the stress-induced hyperthermia. The procedure also measures the intrinsic activity of drugs on the basal body temperature and DeltaT is relatively independent from the intrinsic temperature effects of drugs. Anxiolytic drugs (benzodiazepines, 5-HT(1A) receptor agonists, alcohol) reduce DeltaT suggestive of anxiolytic-like effects. Because the parameter measured for anxiety in the stress-induced hyperthermia procedure is not dependent on locomotor activity, like in almost all other anxiety tests, the stress-induced hyperthermia procedure is an attractive addition to tests in the anxiety field. Because the stress-induced hyperthermia is also present with a comparable pharmacological profile in females, this procedure has a wide species and gender validity. The procedure was applied in various genetically modified mice [5-HT(1A) and 5-HT(1B) receptor knockout (KO) mice and corticotropin-releasing hormone overexpressing (CRH-OE) mice] to study phenotypic influences of the various mutations on aspects of anxiety. The stress-induced hyperthermia test in singly housed male and female mice appears a useful and extremely simple test to measure effects of drugs on certain aspects of anxiety or to help to determine phenotypic differences in mutant mice.
European Journal of Pharmacology 03/2003; 463(1-3):117-32. · 2.52 Impact Factor
