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Biomedical subjects

A M van der Poel

Publications and source records attributed to A M van der Poel.

At least 19 recordsLinked to original sources
PubMed1996

Reduction of guinea pig pup isolation calls by anxiolytic and antidepressant drugs.

Guinea pigs possess central 5-HT1D receptors similar to humans but different from rats and mice. In order to study the role of this receptor on animal behaviour, it may be of interest to develop a paradigm measuring affective states in the guinea pig. Therefore we assessed the effects of a variety of psychotropic drugs on guinea pig pup isolation calls. Anxiolytic compounds such as the benzodiazepine receptor agonists diazepam and alprazolam, the full 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan, and alcohol reduced isolation calling by the guinea pig pup. Moreover, mixed antidepressant/anxiolytic compounds like the 5-HT uptake inhibitors fluvoxamine and clomipramine or the MAO-inhibitor clorgyline as well as the antidepressant NA uptake inhibitors desipramine and maprotiline suppressed vocalizations. The 5-HT1D/1A receptor agonist 5-CT was also very effective in reducing separation calls. Remarkably, the partial 5-HT1A receptor agonists buspirone and BMY 7378 did not affect calling. The neuroleptic haloperidol, the psychostimulant d-amphetamine, the putative anxiogenics DMCM and m-CPP and the putative anxiolytics ondansetron and CI-988 had no effect on isolation calls of guinea pig pups. We propose this paradigm could be helpful to assess behavioural effects of anxiolytic and antidepressant drugs in a species different from rat or mouse, and in which the effects of 5-HT1D receptor ligands may possibly be established.

Animals↗
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

The ambivalent behaviour "stretched approach posture" in the rat as a paradigm to characterize anxiolytic drugs.

The effect of various psychotropic drugs on the ambivalent behaviour "stretched approach posture" (SAP) in the rat was assessed. SAP was elicited after a mild startle reaction due to physical contact with an electrified prod at one end of a straight runway. Using ethological observation methods, SAP as well as intention movements, prod contact, crossings, rearing, exploration, grooming and immobility were recorded. The benzodiazepine receptor agonists chlordiazepoxide, diazepam and alprazolam, the 5-HT1A receptor agonists flesinoxan and ipsapirone and the 5-HT uptake inhibitor clomipramine selectively (no effect on crossings) reduced SAP. Except for alprazolam, these drugs also reduced intention movements. In addition, chlordiazepoxide and diazepam enhanced prod contact. Reductions of SAP and intentions with concomitant reductions of crossings (nonspecific antiambivalent effects) were established for the alpha 2-adrenoceptor agonist clonidine and the MAO inhibitor clorgyline. The 5-HT uptake inhibitor fluvoxamine suppressed intention movements, but not SAP. The mixed 5-HT/NA uptake inhibitor imipramine did not significantly affect SAP or intentions, but reduced crossings. The 5-HT2C/1B receptor agonist m-CPP, the inverse BZD receptor agonists FG 7142 and DMCM, and the alpha 2-adrenoceptor antagonist yohimbine, to all of which putative anxiogenic effects have been ascribed, had no effect on SAP directed towards the prod. m-CPP, however, produced an increase in the stretched posture directed away from the prod (SAwayP). FG 7142 reduced intentions while strongly enhancing immobility (freezing). SAwayP and/or freezing may possibly reflect anxiogenic properties of drugs. The putative anxiogenic drug pentylenetetrazol false positively reduced SAP while increasing exploration. The dopamine-D2 receptor antagonist haloperidol and the catecholamine releaser dl-amphetamine had no effect on ambivalent behaviour. The muscarine receptor antagonist scopolamine reduced SAP and intentions while stimulating crossings. Finally, the 5-HT2C receptor antagonist ritanserine, the CCKA receptor antagonist devazepide, the CCKB receptor antagonist L-365.260 and the strychnine-insensitive glycine site antagonist 7-Cl-kynurenic acid were without effect on the behaviours in this paradigm using single doses. In conclusion, SAP and intention movements were reduced selectively by anxiolytic agents from different classes, including benzodiazepine receptor agonists, 5-HT1A receptor agonists and a 5-HT uptake inhibitor, whereas an alpha 2-adrenoceptor agonist and a MAO inhibitor reduced SAP non-selectively. SAP in relation to other behaviours may therefore serve as a valuable paradigm to characterize anxiolytic drugs.

Alprazolam↗
PubMed1989

Temporal patterning of ultrasonic distress calls in the adult rat: effects of morphine and benzodiazepines.

Opioids and benzodiazepines modulate the ultrasounds that rats emit before being presented with aversive stimulation. Mild, intermittent 10 s electrical tail stimulation induces rats to emit 20-30 kHz ultrasounds before and after the stimulation. Analysis of the temporal parameters of the sounds via a customized computer system reveals them to be emitted in bouts of about five sounds, each sound being separated from the next by 0.2-0.35 s pauses. Morphine decreases the per cent time vocalizing during the pre-stimulation period, with 6 mg/kg being fully suppressive. This effect is reversed by 1 mg/kg naloxone pre-treatment. Chlordiazepoxide and morphine have opposite effects on the temporal structure of the pre-stimulation calls; chlordiazepoxide induces longer bouts with more pulses, and morphine dissolves the bout structure into a series of single pulses. These differential and selective effects of morphine and benzodiazepines on the occurrence and temporal structure of ultrasounds may be relevant to characteristics of different affective expressions.

Animals↗
PubMed1988

Hypothalamic substrates for brain stimulation-induced patterns of locomotion and escape jumps in the rat.

The hypothalamic response area for electrically induced locomotion was determined using moveable electrodes and discriminant analysis as an appropriate statistical technique. At 241 out of 641 stimulated sites locomotion was induced. The distribution of locomotion sites is relatively diffuse. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probability of inducing the response. The response is considered to be mediated by fibres of the subpallido-pedunculopontine system, which includes the mesencephalic locomotor region. Different categories of exploratory and flight-directed locomotion were distinguished, and response areas for both categories were determined. In addition the response area for escape jumps was delimited. Exploratory locomotion is mainly induced from the lateral hypothalamus, while flight-directed locomotion and escape jumps are evoked from the medial hypothalamus. The response area for exploratory locomotion reflects the lateral hypothalamic distribution of the subpallidal projection to the mesencephalic locomotor region. A diffuse substrate for flight behavior seems to occupy almost the entire medial hypothalamus. It is concluded that a locomotor subroutine subserving different behavioural mechanisms can be activated at many hypothalamic sites.

Animals↗
PubMed1988

Hypothalamic substrates for brain stimulation-induced attack, teeth-chattering and social grooming in the rat.

In this paper the boundaries of the hypothalamic response areas for brain stimulation-induced attack, social grooming and teeth-chattering were delimited. A total of 641 hypothalamic sites in 71 male CPW/WU Wistar rats were electrically stimulated. Positive sites for any behavioural response cluster into restricted hypothalamic areas. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate and low probabilities of inducing the behavioural response concerned. Each response has its own response area where probabilities are high. Neuroanatomical correlates of these response areas are discussed. The response area of attack is suggested to be an integrative processing area, stimulation of which overrules some aspects of integration and directly activates the behavioural program of attack. Although some authors consider all three responses to be part of the behavioural repertoire of aggression, the response areas are not identical. Social grooming and attack are considered to be induced from different neural systems. Similarly, attack and teeth-chattering have been shown to derive from different neural mechanisms, despite substantial overlap of both response areas. It is suggested that teeth-chattering derives from the simultaneous activation of both attack and flight tendencies. No further distinctions with respect to threshold current intensities can be made within responses areas. However, the underlying neural substrates are not homogeneous, for thresholds vary along the course of individual electrodes.

Aggression↗
PubMed1987

Hypothalamic substrates for brain stimulation-induced grooming, digging and circling in the rat.

Despite a great number of studies concerned with the induction of specific behavioural responses from the rat hypothalamus by electrical brain stimulation, hypothalamic response areas and underlying neural substrates have never been determined accurately. In this study the boundaries of the hypothalamic response areas for grooming, digging and circling were delimited using moveable electrodes, an enriched environment containing a variety of goal objects, and an appropriate statistical technique. A total of 641 hypothalamic sites in 71 male CPB/WU Wistar rats were electrically stimulated. Results are plotted on a detailed stereotaxic brain atlas of the rat hypothalamus. Positive sites for any behavioural response cluster into restricted hypothalamic areas. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probabilities of inducing the behavioural response concerned. Each response has its own response area where probabilities are high, although there may be overlap. Even within response areas a distinction can be made between areas in which the response can be induced at relatively high or low threshold current intensities. Lowest threshold sites within electrode tracks are often clustered. In search of neuroanatomical correlates, grooming is related to the distribution of ACTH-immunoreactive neural elements, digging is related to the distribution of efferent fibres from the bed nucleus of the stria terminalis, and circling is related to the distribution of dopaminergic fibres of the nigrostriatal pathway. The results clearly point to the stimulation site being the most important determinant of the evoked behavioural response. Evidently behavioural specificity does exist within the hypothalamus.

Animals↗
PubMed1987

Postpartum aggression in rats does not influence threshold currents for EBS-induced aggression.

Female Wistar rats were tested for aggressive behaviour induced by electrical brain stimulation (EBS) in the lateral hypothalamus. Threshold currents for the induction of aggression were determined on several days before the females were paired with experienced breeder males. Beginning in the second week of pregnancy threshold current values were measured once or twice weekly. No change in thresholds was observed either during pregnancy, the early postpartum period or after weaning. Lactation was the only period during which the females were spontaneously aggressive towards male intruders in their home cage, but not in the EBS cage. Analysis of bite targets revealed no difference between the bite patterns in the postpartum maternal aggression test and the EBS-induced attacks. The results demonstrate that the change in physiological and hormonal status in pregnant and lactating females has no influence on the propensity to attack during EBS. The similarity in wound patterns does not advocate a major difference in the types of aggression studied. We speculate upon the nature of EBS-induced attacks as the activation of a rigid, final pathway of aggression which is rather insensitive to mild modulations.

Aggression↗
PubMed1987

Modulatory actions of benzodiazepine receptor ligands on agonistic behaviour.

Several experiments were conducted to establish the role of benzodiazepine (BDZ) receptor ligands in aggressive behaviour in male and female rats. In particular, the pro-aggressive effects of BDZ agonists was subject of investigation. Predatory aggression (mouse killing) was facilitated by chlordiazepoxide (CDP) when tested in naive female rats, but CDP was unable to induce muricide in non-killing rats with extensive experience with mice. In experiments on maternal aggression in rats a post-hoc analysis revealed that the pro-aggressive action of CDP on maternal aggression was base line dependent: the increase in aggression in spontaneously low aggressive females was significantly higher than in females with a higher base line level. A further study aimed at unravelling the underlying factors contributing to this pro-aggressive action by determining the role of opponent size on the effects induced by CDP. Normally large opponents evoke less aggression from lactating females than smaller opponents and CDP exerted its pro-aggressive effect particularly strongly in the 'large opponent' situation. An ethological analysis was made of lateral display--an ambivalent posture frequently occurring in agonistic behaviour--to establish whether CDP indirectly increases aggression by reducing fear by means of its anxiolytic properties. The data partly support this hypothesis. These findings stress the importance of environmental and experiential factors in the possible outcome of CDP effects on aggression. Moreover, they point to possible explanations of seemingly contradictory data. In two final experiments an inverse benzodiazepine receptor agonist (beta-CCE) was tested in maternal aggression. beta-CCE reduced aggression, although not in a completely specific way. A neutral BDZ-receptor antagonist (Ro 15-1788) was tried in an attempt to antagonize the pro-aggressive effects of CDP in maternal aggression. Ro 15-1788 did not counteract the pro-aggressive action of CDP, but antagonized CDP effects on exploration. The modulatory role of the benzodiazepine receptor complex in aggression remains an intriguing area of research in which many subtleties in testing conditions play a role and in which more BDZ agonists, inverse agonists and antagonists have to be tested.

Aggression↗
PubMed1983

A locked, non-rotating, completely embedded, moveable electrode for chronic brain stimulation studies in freely moving, fighting rats.

A light-weight, yet rugged moveable electrode assembly is described for chronic brain stimulation studies in small-brained animals. The assembly can be completely embedded in a smooth, unobtrusive dental cement cap and is therefore suitable for use in fighting experiments, where collisions with partners and cage walls will limit the use of other assemblies. It permits a variable electrode distance penetration of 3 mm in 75 mu-steps by using a separate unlocking turning-key. This design excludes the possibility of inadvertent displacement of the electrode tips by the animal itself. Since the electrode itself does not rotate during displacement, extra damage arising from possible eccentricity is avoided. The assembly has been used in a number of hypothalamic penetrations, demonstrating its usefulness and reliability.

Aggression↗
PubMed1982

Aggression induced by stimulation of the hypothalamus: effects of androgens.

Aggressive behavior between male rats induced by electrical stimulation of the hypothalamus (ESH) is stimulated by androgens. This was demonstrated by recording the changes in threshold current intensities (the amount of current needed to induce attack behavior in 50% of the trials), just before castration, after castration, during subsequent treatment with high doses of testosterone propionate, and finally during oil treatment. The results demonstrate that, to induce the same aggressive responses, in absence of androgens more electrical current is needed than when these hormones are present in the general circulation of the ESH stimulated animals.

Aggression↗
PubMed1982

Anti-aggressive effect of a new phenylpiperazine compound (DU27716) on hypothalamically induced behavioural activities.

Using the same hypothalamic electrodes, the following behaviour was evoked in male rats by electrical stimulation at roughly equal current intensities: attacks on a partner, teeth-chattering, switch-off behaviour and locomotion. Current thresholds were determined for each behaviour following the intraperitoneal administration of saline or DU27716, a new phenylpiperazine compound with interesting inhibitory effects on territorial and intermale aggression. DU27716 raised current thresholds for attack and teeth-chattering beginning at the lowest dose (4 mg/kg), whereas there was no effect on switch-off behaviour, and only a slight but significant effect on locomotion thresholds at the highest dose (8 mg/kg). The results provide support for the hypothesis that DU27716 possesses behaviourally selective, anti-aggressive properties, and illustrate the usefulness of hypothalamically induced behaviours as a pharmacological model.

Aggression↗