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Biomedical subjects

J M van Ree

Publications and source records attributed to J M van Ree.

At least 37 records · Page 2Linked to original sources
PubMed2000

Odor discrimination and task duration in young and older adults.

The effect of task duration on odor discrimination in aging was studied. Twenty-seven young male adults and 24 young female adults between 18 and 30 years of age, and 17 older male adults between 45 and 65 years of age completed an odor discrimination task. The odor discrimination task consisted of two parts of 16 trials each in which, from three bottles consisting of two identical and one aberrant odor, the aberrant odor had to be identified. The two parts were identical except that the aberrant odor was interchanged with the identical odors in the second as compared with the first part. Results revealed a decrease in odor discrimination with age. Moreover, with increased task duration odor discrimination performance decreased considerably in older male adults while it remained unchanged in young male adults. In addition, in young adults a small advantage in females as compared with males was found in the first part of the odor discrimination task, but this effect disappeared with increased task duration. In conclusion, task duration should be taken into consideration as a factor influencing odor discrimination in aging.

Adolescent↗
PubMed1999

Short and long term plasticity after lesioning of the cell body or terminal field area of the dopaminergic mesocorticolimbic system in the rat.

To investigate within one study regenerative capacities of dopaminergic axons and cell bodies, short and long term recovery of behavioral and biochemical impairments following a bilateral 6-hydroxydopamine (6-OHDA) lesion of the ventral tegmental area (VTA)-nucleus accumbens (NAc) pathway was investigated in rats. Novelty-induced motility, presynaptic functions and the levels of dopamine (DA) and its metabolites were reduced when cell bodies in the VTA or axons in the NAc were lesioned. Spontaneous recovery of the behavioral deficit was observed 4 weeks after a lesion of the NAc. Subsequently presynaptic functions recovered as shown by the reappearance of low dose apomorphine (50 mg/kg)-induced hypomotility, normalization of [(3)H]dopamine uptake, reinnervation of the NAc and normalization of levels of DA and its metabolites within 24 weeks. In contrast, after a VTA lesion no recovery was observed during 48 weeks, neither from hypomotility and loss of the low dose apomorphine response nor from decreased [(3)H]dopamine uptake and levels of DA in the NAc. Short term postsynaptic supersensitivity (hypermotility upon a higher dose of apomorphine (125 mg/kg)) was present 1 and 4 weeks after the lesion but not thereafter. A near total absence of dopaminergic neurons in the VTA and axons in the NAc were found 24 weeks postlesion. Treatment with the ACTH-(4-9) analog ORG 2766 (10 mg/kg s.c., 6 days once daily) facilitated recurrence of presynaptic functions after a lesion of axons but had no short or long term effect when cell bodies were lesioned. These findings substantiate the postulate that the peptide facilitates recovery processes.

Adrenocorticotropic Hormone↗
PubMed1999

P50 suppression and prepulse inhibition of the startle reflex in humans: a correlational study.

BACKGROUND: Sensory gating is an important feature of the normally functioning brain. When not operating correctly, it can contribute to different kinds of psychiatric illnesses by flooding the higher brain functions with useless information. Over the years, two paradigms have evolved to quantify the amount of sensory gating: the prepulse inhibition (PPI) of the startle reflex and the suppression of the P50 evoked potential. To enable comparison across studies it is important to find out to what extent these paradigms reflect the same processes. In the present study, this relationship was explored. METHODS: Thirty-one healthy male volunteers with no personal or family history of mental illness were tested on their ability to suppress the P50 wave and to inhibit the startle reflex. RESULTS: A significant positive correlation was found between PPI and P50 suppression mainly early in testing, when habituation of the startle reflex is taking place. Furthermore, a significant negative correlation was found between P50 suppression in the second half of testing and the habituation of the startle reflex. CONCLUSIONS: PPI and P50 suppression are correlated at an early stage of testing, when the process of habituation of the startle reflex is active. The role of the habituation in the correlation between these two measures needs to be further explored.

Acoustic Stimulation↗
PubMed1999

A heroin-, but not a cocaine-expecting, self-administration state preferentially alters endogenous brain peptides.

The purpose of the current study was to assess neuropeptidergic alterations during a phase of the drug addiction cycle associated with drug craving as compared to a time period when the drug had been recently self-administered. Male Wistar rats were allowed to self-administer cocaine, heroin or saline for 6 h for 5 consecutive days. Immediately following the last self-administration session ('acute drug on board' state), and just before the next scheduled session ('drug expecting' state), the animals were decapitated and the levels of dynorphin A and B, [Met5]- and [Leu5]-enkephalin and substance P were measured in different brain areas. During the 'acute drug on board' state, peptide levels in animals that self-administered heroin or cocaine were not significantly changed. In contrast, during the 'drug expecting' state, heroin-treated animals had increased levels of dynorphin A, dynorphin B and [Met5]-enkephalin in the caudal striatum as compared to the cocaine- and saline-treated animals, and the level of [Leu5]-enkephalin was increased as compared to the cocaine-treated group. In the septum, an increase of [Met5]-enkephalin and substance P was observed in the animals expecting heroin as compared to the saline- and/or cocaine-treated animals. In the caudal striatum, substance P levels were elevated in the heroin- and cocaine-expecting animals. In conclusion, heroin, as compared to cocaine, appears to have a more pronounced effect on dynorphin, enkephalin and substance P levels in the caudal striatum and septum, especially during periods when self-administration of the drug is expected.

Animals↗
PubMed1999

Social behavior of juvenile rats after in utero exposure to morphine: dose-time-effect relationship.

In the present study, the effects of morphine exposure in utero on social behavior in juvenile male rats was investigated. Pinning, a measure for play behavior, and social grooming of the offspring were measured at postnatal day 21. The subjects were offspring of Wistar rat dams given sc. injections of 1 or 10 mg/kg body weight morphine HCl daily from gestational days 8 (GD8)-GD 21 and control dams injected daily with saline. Pinning and social grooming of the morphine-treated offspring were significantly elevated compared to saline controls. The doses of morphine used neither affected the gestation of pregnant mother rats nor sensorimotor development of the juvenile rats. Prenatal exposure to morphine of 10 mg/kg daily increased both pinning and social grooming, prenatal exposure to a lower dose of 1 mg/kg increased pinning behavior but not social grooming in the offspring. To study the importance of the gestational period, offspring of dams given 10 mg/kg body weight morphine HCl from GD8-GD15 and saline from GD16-parturition or morphine from GD16-parturition and saline from GD8-GD15 was tested. Pinning was only increased when morphine exposure occurred during the third week of gestation, social grooming was increased when morphine exposure had been in the second week of gestation. Subcutaneous administration of 1 mg/kg naltrexone 1 h before the test significantly decreased play behavior in control rats, but not in animals prenatally exposed to morphine. From these experiments we conclude that the long term effect of in utero exposure to morphine on play behavior is established by affecting the endogenous opioid system.

Age Factors↗
PubMed1999

D-cycloserine increases positive symptoms in chronic schizophrenic patients when administered in addition to antipsychotics: a double-blind, parallel, placebo-controlled study.

A hypofunction of the glutamatergic system and NMDA receptors in schizophrenia has been hypothesized. Therefore, stimulation of these receptors could be of benefit to patients with schizophrenia. D-cycloserine has been used for this purpose. This study reports the effects of 100 mg D-cycloserine, when added to typical antipsychotics in chronic schizophrenic patients exhibiting prominent negative symptoms, using a placebo-controlled, double-blind, parallel, design. D-cycloserine slightly worsened psychotic symptoms and general psychopathology as compared to placebo. D-cycloserine failed to change negative symptoms and had no effect on extrapyramidal symptoms. The exacerbation of schizophrenic symptoms may be explained by the antagonistic effects of this dose of D-cycloserine at the glycine recognition site of the NMDA receptor due to competition with the endogenous agonist glycine. Another explanation for the increase in psychopathology may be an interaction with the effects of antipsychotics on NMDA mediated neurotransmission. Thus, D-cycloserine in this study did not ameliorate schizophrenic symptoms. However, the fact that they actually worsened suggests that NMDA systems may be involved in the pathogenesis of schizophrenia. Further placebo-controlled studies with lower dosages of D-cycloserine, preferably in drug-free patients, are necessary to evaluate if D-cycloserine is of use for the treatment of patients with schizophrenia.

Adult↗
PubMed1999

Responses to median and tibial nerve stimulation in patients with chronic neuropathic pain.

Somatosensory evoked magnetic fields and electrical potentials were measured in eight patients with unilateral neuropathic pain. After median nerve stimulation on the painful side, the amplitudes of the evoked responses were enhanced 2 to 3 times at a latency of about 100 ms compared to the responses of the contralateral, unaffected side. After posterior tibial nerve stimulation an enhancement was found at latencies around 110 ms and 150 ms. The scalp distribution of the magnetic field at the latencies of "abnormal" responses was dipolar and the responses could be ascribed to a current dipole. Three (of the eight) patients underwent spinal cord stimulation (SCS) for their pain. The enhancement of the evoked responses to stimulation of the painful side decreased after spinal cord stimulation. After a long period of spinal cord stimulation only (e.g., a year) during which the patient reported to be pain free, these "abnormal" responses were no longer observed.

Accidents↗
PubMed1998

The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects.

Recently, much interest has been given to the role of glutamatergic N-methyl-D-aspartate receptors (NMDA) in sensory gating, such as prepulse inhibition (PPI) and reduction of the P50 evoked response potential (ERP). Currently, mainly animal data are available describing the role of NMDA receptors in these stimulus evaluation processes. Human data are virtually lacking and are potentially important, for instance for the understanding of sensory gating deficits observed in schizophrenia. Therefore, the effects of the NMDA antagonist ketamine, in a dose of 0.3 mg/kg i.v., on concurrent assessment of PPI and P50 reduction was studied in 18 healthy male volunteers. Ketamine was administered in a pseudo-steady state model with a subacute loading dose. In addition, the effects of ketamine on behavior, vital signs, homovanillic acid (HVA) plasma levels and secretion of cortisol and luteinizing hormone (LH) were also determined. Ketamine did not significantly alter PPI or the reduction of the P50 ERP. A small but significant increase in Brief Psychiatric Rating Scale (BPRS) total scores and BPRS composite scores "thinking disorder" and "withdrawal/retardation" was observed. Several subjects experienced visual perceptional alterations, but complex hallucinations did not occur. Ketamine induced mild analgesia and coordination problems. In addition, ketamine induced a marked rise in cortisol secretion, while LH secretion was not affected. Finally, systolic and diastolic, blood pressure and heart rate increased during ketamine infusion. Although in humans NMDA receptors may not be involved in the regulation of PPI and P50 reduction, the most likely explanation for the lack of effect of ketamine on these sensory gating paradigms is the dose used in this experiment. However, using a higher dose is hampered by the aspecificity of racemic ketamine. Future studies should use the enantiomer S-ketamine, which is more specific to NMDA receptors, to evaluate the involvement of NMDA receptors in these neurophysiological processes further.

Adult↗
PubMed1998

The partial NMDA agonist D-cycloserine stimulates LH secretion in healthy volunteers.

D-Cycloserine, a partial agonist of the glycine recognition site of the N-methyl-D-aspartate (NMDA) receptor, may serve as a probe for human cerebral NMDA receptor function. Since NMDA receptors are involved in neuroendocrine secretion, changes in pituitary secretion in response to D-cycloserine administration could serve as a model for NMDA receptor activity. The effects of an oral dose of 500 mg D-cycloserine were assessed in a neuroendocrine challenge paradigm in 20 healthy male volunteers, using a double-blind, randomized placebo-controlled crossover design. Luteinizing hormone (LH) and cortisol secretion was studied, since preclinical studies indicate that these hormones increase in response to NMDA receptor stimulation. Furthermore, plasma homovanillic acid (HVA) secretion was studied, as NMDA receptors are suggested to be involved in the regulation of dopaminergic neurotransmission. D-cycloserine was readily absorbed and did not induce side-effects or changes in vital signs and mood scores. D-Cycloserine stimulated LH secretion and induced a significant rise of the area under the plasma concentration time curve of LH. D-Cycloserine did not stimulate cortisol or plasma HVA secretion. These neuroendocrine effects suggest that D-cycloserine may be used to assess human NMDA receptor function in cerebral disorders, such as schizophrenia.

Adult↗
PubMed1998

Neurohypophyseal peptides and social recognition in rats.

An encounter between rats results in bouts of social investigation consisting mainly of sniffing, nosing, following and grooming. The assessment of social recognition is based on the tendency of rodents to investigate unfamiliar conspecifics more intensely, than familiar ones. In the laboratory an immature conspecific is normally used as the social stimulus because the use of juveniles eliminates possible sexual and/or aggressive behaviors of the rat whose memory is assessed. When a juvenile is presented for the first time, it is intensely investigated. A second presentation shortly after the first one elicits less attention. This is not due to satiation or fatigue, since the presentation of a novel juvenile triggers the full sequence of investigation. Social recognition is defined as a specific decrease in social investigation during the second encounter of the same individual. This form of memory is short lasting (< 40 min) and based on the olfactory characteristics of the stimulus animal. Social memory is prolonged by repeated exposure to the stimulus juvenile rat and is impaired by retroactively interfering stimuli. It can be facilitated by vasopressin and derivatives as well as by several other memory facilitating compounds, and, depending on the dose, attenuated or facilitated by oxytocin and derivatives. Ethologically oriented memory tests, that are based on olfactory characteristics of the information to-be-remembered, have an advantage over 'classical' ones: they estimate behavioral patterns which are important to an animal and not only to the investigator. Social memory paradigms can reveal information about memory processes in animals that is relevant for memory deficits in humans.

Animals↗
PubMed1998

Vasopressin metabolites: a link between vasopressin and memory?

The effects of endogenous metabolites of the neuropeptide vasopressin (VP) in behavioural tests led to the hypothesis that VP metabolites have a more selective function than VP. In contrast to VP, no peripheral effects have been found thus far with VP metabolites and their function seems to be associated with memory-related behaviour. VP metabolites can improve both consolidation and retrieval of memory. Effects on autonomic and electrophysiological parameters and interactions with other neurotransmitter systems have provided some information about the processes that could underlie the effects of VP metabolites on memory-related behaviour. There is evidence that the effects of VP metabolites could be mediated by a VP metabolite receptor, which is different from the known VP receptors. The VP metabolite receptor could be a link between the neuropeptide VP and memory-related behaviour.

Animals↗
PubMed1998

Effects of context on judgements of odor intensities in humans.

This study evaluated whether the intensity of previously smelled odors could unintentionally influence the subsequent judgement of odor intensity. The predicted context effect was based on the adaptation-level theory. Before and 25 min after either WEAK or STRONG biasing odor concentrations, 51 subjects were required to rate the intensity of 10 different odor concentrations of California Orange Oil. After the WEAK bias, subjects judged the odor intensity as being stronger than they did after the STRONG bias. Thus the intensity of odors smelled 25 min earlier can unintentionally influence subsequent odor intensity judgement. The findings are discussed in the light of two alternative explanations, namely, a central implicit memory process and a stimulus-level-based change at the peripheral level.

Adolescent↗
PubMed1997

Naloxone inhibits the reinforcing and motivational aspects of cocaine addiction in mice.

The opioid receptor antagonist naloxone is known to influence a wide range of behavioral effects of cocaine, including its addictive property. In the present study the effects of different doses of naloxone and naloxone-methyl-iodide, a methylated analogon of naloxone that does not penetrate the blood-brain barrier, on the action of cocaine in the intravenous self-administration and conditioned place preference (CCP) paradigm were assessed. Systemic naloxone, but not naloxone-methyl-iodide, dose-dependently suppressed cocaine intake during self-administration and decreased the preference for the cocaine-associated compartment in the CCP paradigm. A significant blockade of cocaine's effects was only present at a relatively high dose of NLX (1.0 mg/kg, s.c.). In addition, NLX produced a rightward shift in the inverted U-shaped dose-response curve for cocaine reward during self-administration, indicating a decrease in sensitivity for the reinforcing effects of cocaine. These data demonstrate that blockade of opioid receptors in the brain block both the reinforcing and conditioned motivational effects of cocaine. An interaction between endogenous opioid systems and local dopaminergic systems is suggested in mediating the effects of NLX on cocaine.

Animals↗
PubMed1997

Behavioral and neuroendocrine effects of the partial NMDA agonist D-cycloserine in healthy subjects.

The effect of D-cycloserine, a partial agonist of the N-Methyl-D-Aspartate (NMDA) receptor, were assessed in a (neuroendocrine) challenge paradigm to to examine NMDA systems in male healthy volunteers, using a double-blind, placebo-controlled crossover design. Oral D-cycloserine (15, 50, and 150 mg) was readily absorbed and its plasma concentration increased dose-dependently. Behavioral and hormonal responses were measured for 240 minutes after administration of the drug. D-cycloserine was well tolerated and did not induce side-effects according to the Visual Analog Scales (VAS), the Brief Psychiatric Rating Scale (BPRS) and the Adverse Events Checklist (AEC) & codes. D-cycloserine failed to elicit a neuroendocrine response as evaluated by cortisol, prolactin, and luteinizing hormone (LH) plasma levels. The present result suggests that D-cycloserine can readily be administered to healthy volunteers but that, in the dosages used, neuroendocrine secretion fails to serve as a model for testing NMDA receptor function in humans.

Adult↗
PubMed1996

Sexual motivation: involvement of endogenous opioids in the ventral tegmental area.

The sexual motivation and performance of male rats were observed in a bilevel testing chamber after bilateral infusion of 40 pmol beta-endorphin, 2.75 nmol naloxone or saline into the ventral tegmental area for four succeeding, weekly tests. In the 5 min prior to introduction of the female rat, the male rat explores the bilevel testing chamber. It was previously shown that the increase over tests of these anticipatory level changes is sexually motivated and a response to olfactory stimuli. Naloxone infusion into the VTA prevented the increase of anticipatory level changes. beta-Endorphin failed to affect the anticipatory level-changing behavior. The sexual performance was unaffected by naloxone or beta-endorphin treatment, but the number of ejaculating rats decreased with repeated testing after naloxone treatment. It is concluded that endogenous opioid systems in the ventral tegmental area contribute to the stimulation of sexual motivation and/or reward, presumably by stimulating the mesolimbic dopamine system in response to sex-related olfactory stimuli.

Animals↗
PubMed1996

Effects of ORG-2766 on brain event-related potentials of autistic children.

A double-blind, placebo-controlled study examined the effects of 6 weeks of treatment with the adrenocorticotropin4-9 analogue ORG-2766 (40 mg/day) on brain event-related potentials (ERPs) of autistic children. In visual and auditory oddball paradigms (with task and nontask conditions), standard (80%), target (10%), and unexpected novel stimuli (10%) were presented. ORG-2766 (a) increased the occipital P3 component of the ERP to visual targets, (b) decreased the occipital P3 component of the ERP to auditory targets, (c) did not affect visual and auditory parietal target P3 components, and (d) also did not affect the A/Pcz/300 to auditory novel stimuli. In addition, ORG-2766 treatment increased the N1 component of the ERP to task-irrelevant auditory stimuli.

Adolescent↗