D S Fokkema

University of Groningen, Groningen, Province of Groningen, Netherlands

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Publications (17)45.54 Total impact

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    ABSTRACT: Postpartum blues is thought to be related to hormonal events accompanying delivery. We investigated whether blues-like symptoms depend on the rate of the decline of hormones, by comparing the behavioral consequences of an abrupt versus a gradual decline of gonadal hormones in an animal model. Female rats were treated with estrogen and progesterone for 23 days, administered either by injections or by subcutaneously implanted tubes filled with hormones. A gradual hormone decline was achieved by discontinuation of the injections; and rapid decline by removal of the tubes. Control groups received either a continued treatment or no hormones. In the period following the decline the stress-reactivity was tested with an acoustic startle test on 3 consecutive days, and anxiety behavior with an open-field test on the 2nd day. The Hypothalamus-, Pituitary-, Adrenal-axis (HPA-axis) response to stress was measured by assessing the corticosterone levels and hypothalamic c-fos expression stress-response at the 4th day. The rapid decline of hormones induced an increased startle response lasting for two days, and increased anxiety-like behavior in the open field. This was not found in the gradual-decline and control groups. The HPA-axis response to stress was decreased in all hormone-treated animals. This animal study suggests that: 1) abrupt rather than gradual hormonal changes induce increased stress-reactivity and anxiety-like behavior; 2) postpartum blues may result from differences in the capacity to adapt to the changes of gonadal hormones; 3) Recovery of pregnancy-induced diminished HPA-axis response is independent of the postpartum hormone kinetics.
    Life Sciences 12/2008; 84(3-4):69-74. · 2.56 Impact Factor
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    ABSTRACT: Depression is often preceded by stressful life events and accompanied with elevated cortisol levels and glucocorticoid resistance. It has been suggested that a major depressive disorder may result from impaired coping with and adaptation to stress. The question is whether or not hypothalamus-pituitary-adrenal (HPA)-axis dysfunction influences the process of adaptation. We examined the effect of a dysregulated HPA-axis on the adaptation to acoustic stimuli in rats with or without preceding restraint stress. HPA-axis function was altered via slow release of corticosterone (CORT, 90 mg) from subcutaneously implanted pellets for 7 or 14 days. The rate of body temperature increases during restraint (10 min) and the response to acoustic stimuli (of 80+120 dB) were used to quantify daily stress reactivity. Rats habituated to either stress regardless of CORT treatment. CORT treatment combined with restraint decreased the initial reactivity and the variability in response, but the rate of habituation was not influenced. These results show that suppressing normal HPA-axis function by chronic exposure to CORT does affect the course of habituation, but not habituation per se. This implies that altered HPA-axis function in depressed patients may not be causally related to stress coping, but instead may influence the course of the disorder.
    Life Sciences 08/2008; 83(3-4):135-41. · 2.56 Impact Factor
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    ABSTRACT: The neurotransmitter glutamate and its associated receptors perform an important role in the brain circuitry underlying normal fear processing. The glutamate NMDA receptor, in particular, is necessary for the acquisition and recollection of conditioned-fear responses. Here the authors examine how acute blockage of the NMDA receptor with sub-anaesthetic doses of ketamine affects behavioural assays of fear-conditioned stress (e.g. freezing) and cFos expression in a network of brain areas that have previously been implicated in fear processing. Fear-conditioned rats displayed significantly more freezing behaviour than non-conditioned controls. In fear-conditioned rats that also received ketamine, this conditioning effect was largely neutralised. Fear conditioning also led to increased cFos expression in various areas central to fear processing, including the basolateral nucleus of the amygdala, the paraventricular nucleus of the hypothalamus and the anterior cingulate. Ketamine abolished such increases in cFos expression in most brain areas investigated. The present study therefore demonstrates that systemic ketamine administration in rats interferes with fear conditioning on a behavioural level and in a network of brain regions associated with fear and anxiety. The combination of ketamine and fear conditioning may therefore provide a useful model of abnormal fear processing, as observed in certain psychiatric conditions.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 10/2006; 30(7):1209-18. · 3.55 Impact Factor
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    Gabor Imre, Dirk S Fokkema, Gert J Ter Horst
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    ABSTRACT: Acute treatment with LY354740 {1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate}, a potent and selective agonist for group II metabotropic glutamate receptors (mGlu2/3), has previously been shown to block some schizophrenia-like effects of N-methyl-D-aspartate (NMDA) receptor antagonists, suggesting a novel therapeutic strategy for schizophrenia. The present study examined the effects of subchronic pretreatment with LY354740 (0.3, 3 and 10 mg/kg i.p.) on ketamine-evoked (12 mg/kg s.c.) prepulse inhibition deficits, hyperlocomotion and c-fos expression. At all doses, LY354740 failed to reverse both behavioral and neuronal effects of the ketamine. These results therefore do not support the putative antipsychotic role of LY354740.
    European Journal of Pharmacology 09/2006; 544(1-3):77-81. · 2.59 Impact Factor
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    ABSTRACT: One of the functions of group II metabotropic glutamate receptors (mGluR2/3) is to modulate glutamate release. Thus, targeting mGluR2/3s might be a novel treatment for several psychiatric disorders associated with inappropriate glutamatergic neurotransmission, such as schizophrenia. In an effort to evaluate the antipsychotic properties of LY379268, a potent and selective mGluR2/3 agonist, we examined its effect on ketamine-evoked hyperlocomotion and sensorimotor gating deficit (PPI) in rats, an animal model of schizophrenia. We also measured the ex vivo tissue level of glutamate (Glu), dopamine (DA) and serotonin (5-HT) as well as the DA metabolites DOPAC and the major 5-HT metabolite HIAA to determine the neurochemical effects of ketamine (12 mg/kg) and LY379268 (1 mg/kg) in the dentate gyrus (DG). While LY379268 (1-3 mg/kg) reduced ketamine-evoked hyperlocomotion (12 mg/kg), it could not restore ketamine-evoked PPI deficits (4-12 mg/kg). In the DG we found that ketamine decreased Glu and DA levels, as well as HIAA/5-HT turnover, and that LY379268 could prevent ketamine effects on Glu level but not on monoamine transmission. These results may indicate that the inability of LY379268 to reverse PPI deficits is attributable to its lack of effect on ketamine-induced changes in monoamine transmission, but that LY379268 can prevent ketamine-evoked changes in glutamate, which is sufficient to block hyperlocomotion. In addition to the partial effectiveness of LY379268 in the ketamine model of schizophrenia, we observed a dual effect of LY379268 on anxious states, whereby a low dose of this compound (1 mg/kg) produced anxiolytic effects, while a higher dose (3 mg/kg) appeared to be anxiogenic. Additional work is needed to address a possible role of LY379268 in schizophrenia and anxiety treatment.
    Pharmacology Biochemistry and Behavior 08/2006; 84(3):392-9. · 2.61 Impact Factor
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    ABSTRACT: The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PPI), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined whether ketamine-induced locomotion was influenced by the dark/light cycle. We found that ketamine increased locomotor activity in a dose dependent manner, but found no influence of the dark-light cycle. Additionally, ketamine dose-dependently interrupted PPI, resulting in prepulse facilitation at doses of 8 and 12 mg/kg. The dose of 12 mg/kg also induced impairments in working memory assessed by the discrete-trial delayed-alternation task. C-fos expression indicated that the dose-dependent behavioral effects of ketamine might be related to changes in the activity of limbic regions, notably hippocampus and amygdala.
    Brain Research Bulletin 05/2006; 69(3):338-45. · 2.94 Impact Factor
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    ABSTRACT: Asthma patients have been reported to be sensitive to breathlessness, independent of the degree of airway obstruction. Paying attention and task performance may induce changes in breathing pattern and these in turn may mediate such a feeling. The present experiment investigates whether strained breathing induced by an arithmetic task was different in children with asthma compared to healthy children. Seven healthy and eight asthmatic but symptom-free school children were equipped with electrodes for surface electromyographic (EMG) measurements of diaphragm, abdominal and intercostal (IC) muscles and with a strain gauge to monitor the pattern of breathing at rest and during an arithmetic task. The relative duration of exhalation and the relative speed of exhalation are used as measures of straining. The phase angle of maximal respiratory muscle activities relative to the maximal chest extension (MCE) are additional discriminating parameters. Asthmatic children breathed more slowly and already at rest the phase of their respiratory muscle activity appears to be different. While in healthy children the maximal activity of the (left)abdominal muscles occurred 5+/-29% later than the MCE, in children with asthma the maximal activity occurred 26+/-30% of the cycle earlier than MCE. In children with asthma the activity of the IC muscles starts weaning already at 10+/-30% before MCE, in contrast to the healthy children in which intercostal muscle weaning starts only at 1+/-24% after MCE. During arithmetic, the significant difference between the groups in this respect disappeared. Children with asthma show, even at rest, signs of respiratory muscle straining, probably in order to keep close control over the airflow in a similar way as healthy children during mental tasks. Such a 'careful' breathing pattern may work to prevent airway irritation also when they are free of symptoms.
    Respiratory Medicine 02/2006; 100(1):148-56. · 2.59 Impact Factor
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    ABSTRACT: Social support has a positive influence on the course of a depression and social housing of rats could provide an animal model for studying the neurobiological mechanisms of social support. Male and female rats were subjected to chronic footshock stress for 3 weeks and pair-housing of rats was used to mimic social support. Rats were isolated or housed with a partner of the opposite sex. A plastic tube was placed in each cage and subsequently used as a 'safe' area in an open field test. Time spent in the tube was used as a measurement of anxiety levels. Chronic stress increased adrenal weights in all groups, except for isolated females who showed adrenal hypertrophy in control conditions. In isolated males, chronic stress resulted in an increase in the time the animals spent in the tube. While stress did not affect this parameter in socially housed males, males with a stressed partner showed a similar response as isolated stressed males. Even though adrenal weights showed that isolated females were more affected by stress, after chronic stress exposure, they spent less time in the tube than socially housed females. Socially housed stressed females spent less time in the 'safe' tube compared to control counterparts, indicating that stress has a gender-specific behavioral effect. In conclusion: pair-housing had a stress-reducing effect on behavior in males. Isolation of females was stressful by itself. Pair housing of females was not able to prevent stress-induced behavioral changes completely, but appeared to reduce the effects of chronic stress.
    Hormones and Behavior 06/2005; 47(5):620-8. · 3.74 Impact Factor
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    ABSTRACT: Neuroimaging studies in patients suffering from affective disorders have shown decreased volume and reduced regional cerebral blood flow in multiple areas of the prefrontal cortex, including the medial prefrontal cortex and the orbitofrontal cortex. This aberrant brain activity is among other things attributed to chronic stress. Affective disorders occur more often in women than in men. In the current experiment, female mPFC-lesioned and non-lesioned rats were subjected to 3 weeks of chronic unpredictable stress in order to determine the role of the mPFC in dealing with chronic stress, and the consequences of mPFC damage for coping with consecutive stressful events. mPFC damage in female rats intensified the stress-induced activation of the dorsomedial nucleus of the hypothalamus and the paraventricular nucleus of the hypothalamus as measured with Fos expression changes and markedly increased plasma catecholamine levels after 3 weeks of unpredictable stress. Additionally, an mPFC lesion significantly reduced the time of appearance of stress-induced behavioral changes in the open field. Altogether, mPFC dysfunction affects the way female rats react to chronic stress, it not only increased the activation of brain regions involved in neuroendocrine and autonomic responses to stress but it also significantly reduced the time of onset of behavioral changes.
    Brain Research Bulletin 11/2003; 61(6):627-35. · 2.94 Impact Factor
  • D S Fokkema
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    ABSTRACT: Strained breathing is a natural respiratory pattern, with cardiovascular implications. It is associated with social factors, attention, expectation, and anxiety and with defense behavior in animals. An inhibition of active behavior is characteristic. Strained breathing is based on the functional heterogeneity of the medullary postinspiratory neurons. In stressful circumstances, muscle tension and laryngeal reflexes induce a strong reduction of airflow in the glottis, resulting in a prolonged Stage I of expiration and an elevated intrathoracic pressure. The resulting elevations of blood pressure and CO2 level further stimulate the strained breathing pattern. The straining factor intrathoracic pressure is an important psychophysiological parameter. Functional aspects of strained breathing may be an elevated brain perfusion and the prevention of hyperventilation. It induces blood pressure oscillations and respiratory sinus arrhythmia. Frequent strained breathing may contribute to cardiovascular pathology and sleep apnea, creating a link between functional behavior and disease.
    Psychophysiology 04/1999; 36(2):164-75. · 3.26 Impact Factor
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    ABSTRACT: Previous experiments suggested that rats with an active behavioral strategy and high endocrine and blood pressure responses to social interactions would be at risk to get a high blood pressure. To test this hypothesis, a long-term study of social behavior was performed in laboratory colonies of rats. The more aggressive rats, as indicated by individual precolony resident-intruder tests, are more aggressive in the colony also. After colony aggregation, the aggressive rats appeared to have higher resting blood pressures. The dominant rat (although aggressive, too) and the nonaggressive rats have lower blood pressures. Plasma levels of catecholamines and corticosterone after colony experience do not show a relation with blood pressure but reflect the rat's original precolony aggressive characteristic. We conclude that the individual characteristic of an active social strategy is a risk factor that indeed predicts the development of high blood pressure, possibly by way of the associated higher physiological reactivity we found earlier. Chronic environmental factors that are hard to control for the animal, like involvement in social processes or possibly other continuous challenges, may stimulate the prone physiology to develop an elevation of blood pressure.
    Physiology & Behavior 06/1995; 57(5):857-62. · 3.16 Impact Factor
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    ABSTRACT: Behavioral and physiological responses of 18 chronically cannulated male TMD-S3 rats were assessed during various social interactions with conspecifics, both with and without the possibility for physical contact (social vs. psychosocial stimulation). Response magnitudes (behavior, blood pressure, plasma catecholamines) depend upon both the social environmental requirements (offense, defense, psychosocial stimulus following defense) and individual characteristics. The more competitive males generally reacted with higher responses of blood pressure and catecholamines than more passive rats. In addition, these competitive males had higher baseline levels of noradrenaline. The present experiment shows that male rats differ in the individual sympathetic tone and reactivity in relation to their behavior in a social environment.
    Physiology & Behavior 02/1988; 42(5):485-9. · 3.16 Impact Factor
  • Progress in brain research 02/1987; 72:57-70. · 4.19 Impact Factor
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    ABSTRACT: A large amplitude blood pressure oscillation occurs during social defeat in a territorial fight between male rats, and during the application of a psychosocial stimulus associated with this defeat. Synchronous recording of blood pressure, intrathoracic pressure and diaphragm activity shows that the blood pressure oscillation coincides with a typical respiratory pattern called 'pressure breathing', during which a strongly positive intrathoracic pressure with expiration can be observed. The expiration was relatively prolonged and accompanied by a rise in blood pressure and a decrease in heart frequency. These alterations outlast the applied social respectively psychosocial stimulations. The results of this study suggest that behaviorally induced pressure breathing is of importance to attentional processes during social stimulation. The contribution to the development of hypertension is discussed.
    Life Sciences 03/1986; 38(6):569-75. · 2.56 Impact Factor
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    D S Fokkema, J M Koolhaas
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    ABSTRACT: The naturally occurring tendency to compete with other rats for territorial space has been used to study individual behavior characteristics and blood pressure reactivity to social stimuli in adult male TMD-S3 rats. The competitive characteristics of the individual rats are consistent in two different social situations (victory and defeat). Blood pressure responses during the victory of home territory rats over intruders was more pronounced in the more competitive animals. In addition to defeat by a trained fighter rat, the experimentals were also psychosocially stimulated by the fighter while it was confined in a small wire mesh cage. The blood pressure response to this event was enhanced by the prior defeat of the test animal by the one now confined to the small cage. This response was more pronounced in competitive rats. This approach has potential as an animal model of etiological processes in socially induced hypertension.
    Physiology & Behavior 02/1985; 34(1):33-8. · 3.16 Impact Factor
  • G. Ernsting, D.S. Fokkema
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    ABSTRACT: (1) A significant proportion of unsuccessful attacks by the predator Notiophilus biguttatus (Carabidae) on Orchesella cincta (Collembola) results in damage to the springtails' antennae. (2) Regeneration of the loss occurs at several moults following the amputation, and is attended with an increase in moulting frequency. (3) The regenerated antenna is shorter and always less segmented than normal. (4) The frequency of O. cincta with damaged or regenerated antennae in the field depends on the size (i.e. age) of the springtails. (5) Use of these frequencies in evaluating the role of predators in the dynamics of the springtail population is discussed.
    Netherlands Journal of Zoology 12/1981; 33(4):476-484.
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