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Biomedical subjects

J A Van der Heyden

Publications and source records attributed to J A Van der Heyden.

10 recordsLinked to original sources
PubMed2001

Adaptation and habituation to an open field and responses to various stressful events in animals with neonatal lesions in the amygdala or ventral hippocampus.

A rat model of neurodevelopmental psychopathological disorders, designed to determine neurodevelopmental deficits following damage to the brain early in life, was used to investigate behavioural changes in adaptation and habituation to an open field and responses to different kinds of stressful events. Animals with bilateral ibotenic acid lesions in the amygdala or ventral hippocampus on day 7 or 21 of life were compared to sham-operated animals. According to the model it was assumed that behavioural changes in animals lesioned on day 7, but not in animals lesioned on day 21 of life, were caused by maldevelopment of one or more structures connected to the damaged area. Animals lesioned in the amygdala or ventral hippocampus on day 7, but not animals lesioned in these structures on day 21 of life, displayed decreased (within-session) adaptation and (between-session) habituation to the open field and a decrease in immobility in the forced swim test, whereas only animals lesioned in the amygdala displayed enhanced general activity. These results were indicative of neurodevelopmental deficits. No changes in stress-induced hyperthermia were found, while animals lesioned in the amygdala both on day 7 or 21 of life exhibited decreased conditioned ultrasonic vocalizations. These latter results suggest that the amygdala is implicated in the conditioned stress-induced response. The contribution of the present findings to the animal model of neurodevelopmental disorders like schizophrenia and possible brain structures and neurotransmitter systems involved in the neurodevelopmental deficits are discussed.

Adaptation, Biological↗
PubMed1997

Stress-induced hyperthermia in singly housed mice.

The stress-induced hyperthermia (SIH) paradigm in group-housed mice allows screening of putative anxiolytic drugs. The group-housed SIH was adapted to singly housed animals in order to drastically reduce the number of animals used. The effect of various stressors on rectal temperature was measured in order to find a simple and reliable test procedure. Repeated, but not single disturbance of animals resulted in a strong hyperthermia (deltaT) within 10 min. Similar hyperthermic responses were obtained after immobilization for 1 min or rectal temperature measurement itself. Neither a 120 dB acoustic stimulus, nor repeated 1 mA footshocks led to a temperature change, but 2 mA electric footshocks led to hyperthermia. The final test paradigm chosen involved repeated temperature measurement at a 10 min interval, thus providing both information on basal temperature and deltaT in each animal within a short time frame. Repeated temperature measurements at 10 min intervals revealed a maximum hyperthermia after approximately 30 min, but up to 70% of the hyperthermia is already present 10 min after the first measurement. Repeated use of animals at successive daily or weekly intervals resulted in a gradual increase of both the basal temperature and the temperature 10 min later. At short inter-test intervals (one day) deltaT also decreased, whereas weekly intervals did not affect the amplitude of deltaT. Prior injection of the animals resulted in modest hyperthermia, that returned to baseline after 60 min. The anxiolytics diazepam and 5-HT1A receptor agonist flesinoxan dose-dependently suppressed SIH. The antidepressant amitriptyline lowered temperature levels but did not affect deltaT. The SIH model in singly housed mice appears a fast and reproducible screening test for anxiolytic activity. Compared to the group-housed version, the singly-housed SIH enabled a drastic reduction in the number of animals used.

Amitriptyline↗
PubMed1995

Stress-induced hyperthermia as a putative anxiety model.

In group-housed mice (ten per cage), mice removed last from their home cage always have higher rectal temperatures than mice removed first from this cage. Stress-induced hyperthermia is calculated as the difference (delta T) between the basal temperature (mouse number 1) and the end temperature (mouse number 10) when the temperature of the ten mice is sequentially measured using a 1-min interval between rectal measurements. Using this protocol, various drugs, belonging to different pharmacological classes, were tested in order to investigate their putative anxiolytic effect, measured as a decrease in delta T. Benzodiazepines (diazepam, alprazolam), alcohol, and some (flesinoxan, buspirone), but not all (ipsapirone) 5-HT1A receptor agonists had anxiolytic properties with this protocol. Clonidine (alpha 2-adrenoceptor agonist) and prazosine (alpha 1-adrenoceptor antagonist) had, but at high doses, some anxiolytic actions. Antidepressants (desipramine, fluvoxamine, nomifensine, tianeptine, amitriptyline, clomipramine, imipramine), serotonergic ligands (ondansetron, ketanserin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), fenfluramine, metachlorophenylpiperazine (mCPP), eltoprazine) and various other drugs (phenobarbital, pentetrazol, haloperidol, apomorphine, amphetamine, (+)-N-[1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3( R)-yl]- N'-(3-methylphenyl)urea (MSD 365260), dizocilpine and acetyl salicylic acid) had no anxiolytic activity. The stress-induced hyperthermia protocol used was unable to detect anxiogenic properties of drugs, probably due to a (physiological) ceiling in the maximal end temperature. The stress-induced hyperthermia protocol with mice can be used to measure anxiolytic properties of drugs and is a fast and robust model which does not need extensive training of animals.

Animals↗
PubMed1994

Stress-induced hyperthermia in mice: a methodological study.

When the rectal temperature of group-housed mice is measured sequentially, the temperature of the last measured mouse is higher than that of the first mouse. This phenomenon is called stress-induced hyperthermia (SIH). We varied several experimental parameters to elucidate the mechanism behind this SIH. SIH was stable and found by all technicians performing the experiments. The large intertechnician difference in the mean rectal temperature could be eliminated by training in an identical fixation and handling technique. SIH was both independent of the number of handling days preceding the experiment and of the number of disturbances (0, 1, 2, or 5) implied on the mice per minute. The percentage of hyperthermic mice in 10-mice cages increased when the time interval between the individual measurements increased from 1 to 2, 5 or 10 min. In all groups the maximum increase was reached after an interval of approximately 10 min. SIH of mouse 10 returned time dependently in approximately 60 min to basal temperature. When SIH was tested on 2 or 5 successive days no tolerance developed. When animals were reused after 7 or 14 days SIH did not differ from day 1, implying that animals can be reused. When the number of mice was decreased from 10 to 5 mice per cage, the SIH of vehicle-treated mice was slightly lower in 5-mice cages compared to 10-mice cages. The blocking effects on SIH by anxiolytics was also less clear in 5-mice cages compared to 10-mice cages.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Inescapable footshocks induce progressive and long-lasting behavioural changes in male rats.

Long-term behavioural consequences of exposure to a brief (15 min) session of inescapable footshocks (10 x 6 s, 1 mA) were investigated in male rats. The time course of the effects of inescapable footshocks was assessed by studying the behaviour of groups of rats at different post-stress intervals. Footshocked rats (S) did not differ from control (C) rats (exposed to the shock box for 15 min) in their behavioural response to an open field whether tested 1 h or 4 h post-stress. However, one day after shocks, S rats showed less locomotion and rearing, and more immobility and attention as compared to C rats. At 7 days or 14 days post-stress, S rats exhibited decreased locomotion, rearing, sniffing, and grooming, and increased immobility, attention, and defecation relative to C rats. In a second experiment, we investigated whether footshocks affect the behavioural response to a sudden drop in background noise during exposure to a novel environment. At 21 days post-stress, S rats showed a markedly enhanced immobility response to this stimulus as compared to C rats. In order to investigate whether rats could be exposed repeatedly to the open field without affecting the differences in behaviour between the two treatment groups, C and S rats were tested in an open field for the first time at 7 days post-stress, which yielded the typical effects of footshocks. When these rats were exposed to a second open-field test one week later, the behavioural responses of C and S rats were not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity.

The effects of local injections of drugs into terminal areas of the mesolimbic dopamine system were investigated. Bilateral administration of dopamine, but not of noradrenaline and serotonin, into the nucleus accumbens of non-pretreated rats resulted in stimulation of locomotor activity. No clear or only minor effects were seen after injections of the dopamine metabolites 3-methoxytyramine, DOPAC and HVA and after injections of media with different pH and osmolality. d-Amphetamine proved more effective than dopamine in producing locomotor stimulation, whereas both stimulant and depressant effects were observed following injection of apomorphine into the nucleus accumbens. ET 495 and the noradrenaline agonists clonidine, phenylephrine and isoprenaline did not enhance locomotor activity, but theophylline was effective. Pretreatment with haloperidol, but not with clozapine, significantly reduced the effects of dopamine and theophylline. Locomotor stimulation was also found following bilateral administration of dopamine, d-amphetamine and apomorphine into the tuberculum olfactorium, whereas noradrenaline, serotonin and ET 495 produced no, or rather depressant effects. These results provide further evidence for an important role of the mesolimbic dopamine system with respect to locomotor activity.

Animals↗
PubMed1976

Further investigations on the effects of ergometrine and other ergot derivatives following injection into the nucleus accumbens of the rat.

The influence of different pretreatments upon locomotor stimulation, induced by injection of ergometrine into the nucleus accumbens of rats, was investigated. The noradrenergic antagonists phenoxybenzamine and propranolol and the serotonin antagonist methysergide produced no clear changes. Reserpine, alone or in combination with alpha-MPT, considerably shortened the delay between injection of ergometrine and start of locomotor stimulation. Ro-DOPA, but not Ro-5-HTP, clearly antagonized the locomotor stimulation. The effect of ergometrine was strongly diminished following injection of haloperidol directly into the nucleus accumbens. A strong inhibition was also observedfollowing intracerebral administration of the imidazoline derivative (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI), but not after injection of the structurally related compound clonidine. DPI by itself and also the ergot derivatives ergocornine, bromocryptine, LSD, dihydroergotamine and methysergide in doses 5--10 times as high as that of ergometrine failed to produce locomotor stimulation following injection into the nucleus accumbens. The results are discussed, especially with regard to the role of dopamine.

Animals↗