Biomedical subjects

A R Cools

Publications and source records attributed to A R Cools.

At least 91 records · Page 5Linked to original sources

PubMed1998

[Cognitive deficits in Parkinson's disease].

In neuropsychological studies of Parkinson's disease, cognitive deficits are frequently reported, but the nature of these deficits is not clear. As far as cognitive deficits are manifest in parkinsonian patients at an early stage of the disease, many studies tend to describe them as fitting a frontal syndrome. As a consequence of dysfunction of the striatum, the (pre)frontal cortex receives deficient input from the striatum, which might explain the similarity of the cognitive deficits of parkinsonian patients with those of patients with frontal dysfunction. The present studies provide evidence that the cognitive deficits of parkinsonian patients display a certain similarity with those of patients with frontal dysfunction at the level of the ultimate performance, but that the underlying processes have a distinct character. Parkinsonian patients exhibit a decrease in self-generated problem-solving. This deficit is manifest at a level of cognitive function, which goes beyond task or domain. Among all disease variables, only severity of the disease and especially rigidity proved to be related consistently to this decrease in self-generated problem-solving.

Adult↗

PubMed1997

The role of mesolimbic and nigrostriatal dopamine in latent inhibition as measured with the conditioned taste aversion paradigm.

Repeatedly presenting a non-reinforced stimulus normally retards conditioning to this stimulus when it is coupled to a reinforcer. This phenomenon is called latent inhibition. Since latent inhibition is disturbed after systemic administration of amphetamine, the present study investigated the role of the mesolimbic and nigrostriatal dopamine terminal fields in latent inhibition using a conditioned taste aversion (CTA) paradigm. In this paradigm, a 5% sucrose solution was used as the test stimulus and lithium chloride (LiCl) as the CTA inducing drug. The degree of CTA was assessed by measuring the sucrose preference in a two-bottle sucrose/water choice paradigm 24 h after the LiCl injection. Since conditioned taste aversion has so far not been used to evaluate the role of dopamine in latent inhibition, we first studied the effects of systemic application of amphetamine. The results show that intraperitoneal injections of 0.25 or 0.5 mg/kg d-amphetamine sulphate (given at preexposure and conditioning) significantly disrupted latent inhibition, by selectively reducing sucrose preference in the preexposed group. This could not be attributed to a reduced sucrose intake during preexposure or to a conditioned taste aversion effect of amphetamine itself. In experiment 2 local bilateral administration of 10 micrograms/0.5 microliter amphetamine into the nucleus accumbens or the dorsal striatum was given in the pre-exposed and the conditioning phase, after which the rats were allowed to drink for a fixed period of time. The results show a significant reduction in latent inhibition after intrastriatal, but not after intra-accumbens injections of amphetamine. Intra-accumbens injections of amphetamine, however, significantly reduced fluid intake during preexposure and conditioning. In experiment 3, we therefore repeated this experiment, but allowed the animals to drink only a restricted amount of liquid during preexposure and conditioning. Again the results show a disruption of latent inhibition after intrastriatal, but not intra-accumbens injection of amphetamine. These experiments emphasize the importance of the nigrostriatal dopamine system in the disruption of latent inhibition, at least when using the conditioned taste aversion paradigm. A possible mechanism by which the dorsal striatum might influence latent inhibition is discussed.

Amphetamine↗

PubMed1997

Differences in vulnerability and susceptibility to dexamphetamine in Nijmegen high and low responders to novelty: a dose-effect analysis of spatio-temporal programming of behaviour.

Susceptibility to behavioural effects of dexamphetamine (0.5-2.0 mg/kg, SC) was analyzed in Nijmegen high responders to novelty (HR) and Nijmegen low responders to novelty (LR), using an automated ethological analysis. The main results were that, first, dexamphetamine was more toxic in HR than LR: 5.0 mg/kg dexamphetamine was lethal in 75% HR, respectively, 25% LR. Second, dexamphetamine had effects in HR at doses far lower than in LR: a dose of 0.5 or 1.0 mg/kg dexamphetamine was already sufficient to produce ceiling effects in HR, whereas a minimum dose of 2.0 mg/kg dexamphetamine was required to reach effects of a similar magnitude in LR. Third, the behavioural responses to 2.0 mg/kg dexamphetamine did not differ between HR and LR. These data show that HR are both more vulnerable and more susceptible to the toxic and behavioural effects of intermediate doses of dexamphetamine than LR. It is concluded that knowledge acquired previously about the neurochemical differences between Nijmegen HR (APO-SUS) and Nijmegen LR (APO-UNSUS) rats can be used to analyze further the mechanisms of action underlying individual-specific differences in drug abuse in animals and man.

Animals↗

PubMed1997

Different behavioral effects of daily or intermittent dexamphetamine administration in Nijmegen high and low responders.

Outbred strains of Wistar rats contain both high responders to novelty (HR) and low responders to novelty (LR). Male HR and LR selected from the Nijmegen outbred strain of Wistar rats differ in their sensitivity to acute administration of dexamphetamine (AMPH). Sub-chronic administration of AMPH sensitizes rats to this agent, and this sensitization (SENS) increases when an intermittent, instead of continuous, regimen is used. Thus, the question arose whether HR and LR also differ in the development of sensitization to AMPH. AMPH (0.5 mg/kg SC) was given five times either each consecutive day (daily: DAY) or each alternate day (intermittent: INT). Drug-induced changes in the spatio-temporal patterning of open field behavior were assessed for a period of 45 min. Three sets of data were found: i) in the AMPH-DAY conditions: total number of excursions with 0 stops increased in time: this SENS was far greater in HR than in LR: ii) the effects under AMPH-DAY conditions were far greater that those under AMPH-INT conditions, especially in HR: iii) under AMPH-INT conditions a new phenomenon was observed: following a period in which SENS occurred, a period marked by desensitization appeared which, in turn, was followed by a period with SENS being greater than the SENS seen during the first time; this effect was far more pronounced in HR than in LR. It is concluded that AMPH-INT induces time-dependent changes marked by consecutive periods of SENS and desensitization. This has far-reaching consequences for hypotheses about processes giving rise to the development of (1) SENS to psychostimulants and, consequently, (2) certain aspects of addiction to these drugs.

Animals↗

PubMed1997

Responses to propofol in relation to GABA functionality of discrete parts of the brain of rats.

Genetically-determined regional differences in the GABA-ergic make-up of the brain exist in two lines of Wistar rats viz apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) Wistar rats, Propofol is a GABA-mimetic general anesthetic. This study compared the responses to propofol in APO-SUS and APO-UNSUS rats. Propofol induced a higher incidence of involuntary muscular contractions and oral movements, but a lower incidence of grooming, in APO-SUS rats than in APO-UNSUS rats. Reflex inhibition and narcosis, being defined as the behavior marked by both full absence of purposeful movements and by complete loss of righting reflexes, after propofol did not differ between the two lines. APO-SUS rats had less variation of the heart rates and greater variations of diastolic arterial pressures in response to electrical stimulation than the APO-UNSUS rats, and these variations were reduced by increasing doses of propofol. Arterial pressures in APO-SUS rats were higher than in APO-UNSUS rats. Propofol caused a biphasic change in intra-arterial pressures and had the greatest effect in APO-SUS rats. Differences in cerebral GABA transmission, especially in the striato-nigro-collicular pathway, did not give rise to differences in the effect of propofol on narcosis and hindlimb withdrawal reflex. In contrast, these differences in GABA transmission were accompanied by line-specific differences in effect of propofol on certain behavioral and cardiovascular parameters.

Anesthesia, Intravenous↗

PubMed1997

No major differences in locomotor responses to dexamphetamine in high and low responders to novelty: a study in Wistar rats.

The aim of the study was to compare locomotor responses to acute and sub-chronic dexamphetamine in two distinct types of Wistar rats, namely the Nijmegen high responders to novelty (HR) and Nijmegen low responders to novelty (LR). HR and LR were chosen because they differ in neurochemical processes relevant to the control of the locomotor effects of dexamphetamine, such as the dopaminergic and adrenergic activity in the nucleus accumbens. In experiment 1, a dexamphetamine dose-response curve (0.0-2.0 mg/kg/i.p.) was established using standard activity boxes. The dose-response curve slightly, but significantly, differed between HR and LR: especially the increase elicited by 1.5 mg/kg dexamphetamine was significantly greater in HR than in LR. In experiment 2, locomotor effects of sub-chronic administration of dexamphetamine (1.0 mg/kg/i.p.) were analyzed in HR and LR for 5 consecutive days. HR showed a higher locomotor response to dexamphetamine than LR; however, the two groups did not differ in their sensitization rate. It is concluded that there are neither major HR-LR differences in the locomotor response to acute administration of various doses of dexamphetamine nor HR-LR differences in the rate of sensitization of this locomotor response to sub-chronic administration of dexamphetamine. Type-specific differences in the mutual interaction between corticosteroids and dexamphetamine as well as the nature of the chosen dependent variable, namely locomotor activity, are hypothesized to underlie the results of the present study.

Animals↗

PubMed1997

Plasticity in the stress-regulating circuit: decreased input from the bed nucleus of the stria terminalis to the hypothalamic paraventricular nucleus in Wistar rats following adrenalectomy.

The bed nucleus of the stria terminalis is involved in the stress-regulating circuit by funnelling limbic information to the hypothalamic paraventricular nucleus. Since adrenalectomy influences both limbic structures (by inducing cell death in the hippocampus) and the hypothalamic paraventricular nucleus (by increased corticotrophin-releasing hormone synthesis), we investigated whether the bed nucleus of the stria terminalis is also influenced by adrenalectomy. For this purpose, we analysed and compared the projections from the bed nucleus of the stria terminalis to the hypothalamic paraventricular nucleus in normal and adrenalectomized rats by anterograde tracer injections in the bed nucleus of the stria terminalis. Quantitative analysis of the fibre pattern in the hypothalamic paraventricular nucleus of normal rats revealed a homogeneous distribution of fibres of the bed nucleus of the stria terminalis over the different subdivisions of the hypothalamic paraventricular nucleus. In adrenalectomized rats, the absolute fibre density was significantly lower in the whole hypothalamic paraventricular nucleus (1.17 +/- 0.27 10(-3) microm/microm3 in adrenalectomized rats versus 2.59 +/- 0.24 10(-3) microm/microm3 in normal rats; P < 0.01) and all its subdivisions. The largest decrease of fibre density was found in the corticotrophin-releasing hormone-rich part of the hypothalamic paraventricular nucleus (relative fibre density; adrenalectomized rats: 0.602 +/- 0.106, versus 1.095 +/- 0.019 in normal rats, P < 0.01). These results show a loss of input from the bed nucleus of the stria terminalis to the hypothalamic paraventricular nucleus, and particularly to the corticotrophin-releasing hormone neurons, following adrenalectomy. The data suggest that this pathway within the stress-regulating circuit is functionally affected by corticosteroids in adult rats and may imply that human disorders associated with corticosteroid imbalance are allied to a changed circuitry in the brain.

Adrenalectomy↗

PubMed1996

Movement-related potential measures of different modes of movement selection in Parkinson's disease.

Movement-related potentials were recorded preceding self-paced voluntary movements in patients with Parkinson's disease and in healthy subjects of the same age group. We compared the Readiness Potential preceding joystick movements in a fixed direction and preceding joystick movements in freely selected directions. In normal subjects the Readiness Potential amplitude was higher preceding freely selected movements than preceding movements in a fixed direction. The Readiness Potential in Parkinson patients failed to be modified by the different modes of movement selection. The modulation of the Readiness Potential by different ways of preparing for movement might be due to the supplementary motor area (SMA) being more strongly engaged by tasks requiring internal control of movements than by tasks that are externally structured. The results suggest that this task-dependent variation of SMA activity is reduced in Parkinson's disease. A failing capacity to adapt SMA activity to different task demands has previously been suggested by evidence from positron emission tomography studies using similar tasks.

Adult↗

PubMed1996

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; jaw movements.

The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of jaw movements in rats. When combined with the dopamine D1 receptor agonist (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1- phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine (SKF 82958, 5 micrograms), the putative dopamine D3 receptor agonist (+/-)-7-hydroxy-N, N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 10 micrograms) produced repetitive jaw movements following injection into the shell, but not the core, of the nucleus accumbens. This behaviour was only partially inhibited by local blockade of dopamine D1 receptors (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine, SCH 23390, 500 ng), dopamine D2 receptors (domperidone, 50 and 100 ng) or dopamine D2/3 receptors (l-sulpiride, 25 ng). Combined blockade of both dopamine D1 and D2 receptors in the shell completely antagonized the jaw movements elicited by the cocktail of SKF 82958 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist, S(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[I]benzopyrano[4, 3-b]-1, 4-oxazin-9-ol (PD 128,907, 10 micrograms), in the cocktail did not produce jaw movements, when administered into the shell. Injection of the cocktail of SKF 82958 and 7-OH-DPAT into the ventrolateral striatum, which contains nearly no dopamine D3 receptors, also elicited jaw movements. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific jaw movements: the contribution of 7-OH-DPAT in the cocktail of SKF 82958 and 7-OH-DPAT to the display of jaw movements is solely due to its ability to activate dopamine D2 receptors.

Animals↗

PubMed1996

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour.

The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of turning behaviour in rats. When combined with the dopamine D1 receptor agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7,8-diol (SKF-38393, 5 micrograms), the putative dopamine D3 receptor agonist (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 micrograms) elicited contralateral turning in a dose-dependent manner following unilateral injection into the shell, but not the core, of the nucleus accumbens. The turning pattern displayed was identical to that reported previously after intra-accumbens administration of the cocktail of SKF-38393 and the dopamine D2 receptor agonist quinpirole. The behaviour under study was dose-dependently attenuated by local administration of the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3- methyl-I-phroyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390: 10 and 100 ng), the dopamine D2 receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor antagonist l-sulpiride (5 and 25 ng). Combined blockade of both dopamine D1 and D2 receptors in the shell with a dose of either antagonist alone that produced just a moderate reduction (10 ng SCH 23390 and 50 ng domperidone) completely antagonized the turning behaviour elicited by the cocktail of SKF-38393 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist,S(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4, 3-b]-1, 4-oxazin-9-ol (PD 128,907, 10 micrograms), in the cocktail did produce no turning behaviour at all. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific turning behaviour: the contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the display of turning behaviour is solely due to its ability to activate dopamine D2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1996

Stimulation of acetylcholine or dopamine receptors in the nucleus accumbens differentially alters dopamine release in the striatum of freely moving rats.

The present study examined whether unilateral stimulation of acetylcholine or dopamine receptors in the nucleus accumbens induces an asymmetry in dopamine transmission in the ventrolateral striatum. For this purpose, a microdialysis technique was used to measure dopamine release in both sides of the ventrolateral striatum following unilateral injections of carbachol (5 micrograms/0.5 microliter) or a mixture of dopamine D1 and dopamine D2 receptor agonists (1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7,8-diol 5 micrograms + quinpirole 10 micrograms/0.5 microliter) into the nucleus accumbens. The results show that carbachol injection increased dopamine release in the ipsilateral striatum without changing dopamine release in the contralateral striatum, whereas the dopamine D1/D2 receptor agonist mixture injected unilaterally into the nucleus accumbens produced an increase followed by a decrease in dopamine release in the ipsilateral striatum, but only a decrease in dopamine release in the contralateral striatum. The biochemical effects of the cholinergic treatment greatly outlasted the drug-induced contralateral turning, whereas the biochemical effects of the dopaminergic treatment showed a good correlation with the drug-induced contralateral turning. The present study provides biochemical evidence that unilateral stimulation of acetylcholine or dopamine receptors in the nucleus accumbens elicits an asymmetry in dopaminergic activity in the ventrolateral striatum. The present study also provides biochemical evidence that two distinct neural substrates are involved in the effects of cholinergic and dopaminergic manipulation of the nucleus accumbens.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1996

Development of divergence in dopamine responsiveness in genetically selected rat lines is preceded by changes in pituitary-adrenal activity.

Two pharmacogenetically selected Wistar rat lines have been used as a model for individual variability in behavioral and neuroendocrine responses. As a selection criterion the behavioral responsiveness for the dopamine agonist apomorphine was used, giving rise to the apomorphine-susceptible (apo-sus) and apomorphine-unsusceptible (apo-unsus) rat lines. This selection has been maintained over 16 generations. Recent studies have shown that adult rats of these selection lines also show pronounced differences in responsiveness of the hypothalamic-pituitary-adrenal (HPA) system. In this study we analyzed to what extent the divergence in dopamine phenotype and HPA responsiveness, as observed in adult rats, are linked to possible differences, within both systems, during early postnatal development. Therefore, we measured in neonatal female rats of 10 and 18 days of age several parameters of the dopamine and HPA system which show significant differences in adult rats. These include tyrosine hydroxylase (TH) and dopamine D1 and D2 receptor mRNA levels, which were determined within the nigrostriatal system since this system shows the most pronounced differences between adult rats of both selection lines. As indices of HPA activity we measured CRH mRNA, ACTH and total and free corticosterone plasma concentrations under basal conditions in the morning. Transcripts of the two types of corticosteroid receptors, mineralocorticoid (MR) and glucocorticoid (GR) receptor were measured in hippocampus and paraventricular nucleus. In 10-day-old rats all dopamine and HPA parameters were similar in rats of the two selection lines, except for GR mRNA in the parvocellular neurons of the paraventricular nucleus of the hypothalamus (PVN) of apo-sus rats, which was significantly higher than in apo-unsus rats. Eighteen-day-old apo-sus rats, however, showed significantly higher ACTH, comparable total corticosterone and a trend towards lower free corticosterone plasma levels. This HPA profile resembles the situation in adult apo-sus rats as compared with adult apo-unsus rats. Hippocampal GR mRNA expression and thymus weight were also higher in apo-sus rats. In addition, these rats showed an age-related increase in hippocampal MR mRNA expression, while in apo-unsus rats MR mRNA levels did not change between pnd 10 and 18. The measures of the nigrostriatal dopamine system at day 18 were still similar in rats of both lines. In conclusion, divergence in the dopamine systems of the two pharmacogenetically selected rat lines emerges subsequent to divergence in pituitary-adrenal activity.

Adrenocorticotropic Hormone↗

PubMed1996

Rats bred for enhanced apomorphine susceptibility have elevated tyrosine hydroxylase mRNA and dopamine D2-receptor binding sites in nigrostriatal and tuberoinfundibular dopamine systems.

From a Wistar population two rat lines were generated using as criterion the behavioral response to the dopamine agonist apomorphine. Rats of the apomorphine-susceptible (apo-sus) line revealed a vigorous gnawing response to apomorphine administration while the other rat line, the apomorphine-unsusceptible (apo-unsus) line, was selected for lack of response to the drug. In the present study using the 12th and 13th generation of these genetically selected lines, we have investigated whether this difference in apomorphine responsiveness was correlated with changes in dopamine neurochemistry. Therefore, we measured tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis, as well as dopamine D1 and D2 receptor mRNA levels in discrete brain regions by in situ hybridization. Dopamine (D2/D3) receptor binding was assessed with [125I]iodosulpride in a membrane binding assay and by quantitative autoradiography on tissue sections. [3H]SCH 23390 was used to analyze D1 receptor binding. Apo-sus rats displayed significantly higher TH mRNA levels in the A9 cell group of the substantia nigra pars compacta and in the A12 cell group of the arcuate nucleus. No difference was found in the A10 cell group of the VTA and the A6 cell group of the locus coeruleus. The density of D2/3 binding sites as well as D1 receptor mRNA levels in the striatal projection area of the A9 substantia nigra neurons, were significantly elevated in apo-sus rats. Dopamine D2 receptor mRNA and D1 receptor binding levels in caudate putamen and nucleus accumbens, however, were similar in rats of both lines. In conclusion, high apomorphine susceptibility is related to a potentially enhanced dopamine responsiveness selective for the nigrostriatal and tuberoinfundibular pathways.

Animals↗

PubMed1996

Brain-corticosteroid hormone dialogue: slow and persistent.

1. The stress response system is shaped by genetic factors and life experiences, of which the effect of a neonatal life event is among the most persistent. Here we report studies focused on the "nature-nurture" question using rat lines genetically selected for extreme differences in dopamine phenotype as well as rats exposed as infants to the traumatic experience of maternal deprivation. 2. As key to the endocrine and behavioural adaptations occurring in these two animal models the hormone corticosterone (CORT) is considered. The stress hormone exerts slow and persistent genomic control over neuronal activity underlying the stress response system via high affinity mineralocorticoid (MR) and glucocorticoid receptors (GR). This action is exerted in a coordinate manner and involves after stress due to the rising CORT levels progressive activation of both receptor types. 3. Short periods of maternal separation (neonatal handling) trigger subsequently enhanced maternal care and sensory stimulation. However, a prolonged period (24 h) of depriving the infant of maternal care disrupts the stress hyporesponsive period (SHRP) and causes an inappropriate rise in CORT. During development exposure to CORT and to sensory stimulation has longlasting consequences for organization of the stress response system. 4. We find that these factors embodied by mother-pup interaction are critical for dopamine phenotype, CORT receptor dynamics and neuroendocrine regulation in adult life. The findings provide a conceptual framework to study dopamine-related psychopathology against a background of genetic predisposition, early life events, stress hormones and brain development.

Adrenal Cortex↗

PubMed1996

Contralateral turning elicited by unilateral stimulation of dopamine D2 and D1 receptors in the nucleus accumbens of rats is due to stimulation of these receptors in the shell, but not the core, of this nucleus.

The goal of this study was to determine whether dopamine D2 and/or D1 receptors in the shell and the core of the nucleus accumbens of rats have a differential role in turning behaviour. Unilateral injection of a mixture of the dopamine D2 receptor agonist quinpirole (10 micrograms) and the dopamine D1 receptor agonist 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7, 8-diol (SKF 38393, 5 micrograms) into the shell of the nucleus accumbens produced contralateral turning, when doses which per se were ineffective were injected. This effect was far greater than that found after similar injections into the core of the nucleus accumbens. The effect elicited from the shell was significantly attenuated by prior administration of either the dopamine D2 receptor antagonist l-sulpiride (25 mg/0.5 microliters) or the dopamine D1 receptor antagonist (8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (SCH 23390, 0.5 micrograms/0.5 microliters) into the same region. These data together with the fact that l-sulpiride is known to be a valid tool to differentiate the involvement of distinct regions within the shell underlie the conclusion that dopamine D2 and D1 receptors in the shell, but not the core, of the nucleus accumbens play a critical role in the contralateral turning induced by unilateral injection of dopamine receptor agonists into this nucleus. The results are discussed in view of the known output pathways of the shell.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1996

Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in Nijmegen Wistar rats.

The aim of the study was to investigate the biphasic locomotor response to ethanol in rats. Based on the recent finding that high responders to novelty (HR) and low responders to novelty (LR), selected from an outbred Nijmegen Wistar rat population, show differences in ethanol intake and preference, it was initially investigated to what extent HR and LR differ in their locomotor response to ethanol. A dose-response curve (0.2-2.0 g/kg, i.p.) was established using standardized activity boxes. HR showed a significant increase at 0.5 g/kg, followed by a significant decrease at doses 1.0-2.0 g/kg; LR showed only a decrease at doses 1.0-2.0 g/kg. Secondly, it was investigated to what extent stress altered the ethanol-induced increase and decrease, respectively. For that purpose, the ethanol-induced locomotor effects (0.5 and 1.0 g/kg) were analyzed in habituated and non-habituated (stressed) HR and LR; habituation consisted of a 15-min adaptation period to the activity cages. Stress significantly enhanced the excitatory effects in HR, but had no effect on the sedative effects in HR and LR. Finally, the locomotor effects of sub-chronic treatment (7 days) with an excitatory (0.5 g/kg) or sedative (1.0 g/kg) dose were analyzed in HR and LR. The excitatory effect of 0.5 g/kg disappeared throughout the treatment in HR, whereas the sedative effects of 1.0 g/kg remained the same in HR and LR. It is concluded that the mechanism underlying the ethanol-induced motor excitation differs completely from that underlying the ethanol-induced sedation. Given the known differences in the make-up of the brain and endocrine system between HR and LR, these animals are suggested to be good models for studying the mechanisms underlying the biphasic locomotor response to ethanol in rats.

Animals↗

PubMed1996

Dipole source analysis suggests selective modulation of the supplementary motor area contribution to the readiness potential.

The readiness potential preceding voluntary movement is modulated by the mode of movement selection, i.e. it has a higher amplitude preceding freely selected than before prescribed movements (Praamstra, P., Stegeman, D.F., Horstink, M.W.I.M., Brunia, C.H.M. and Cools, A.R. Movement-related potentials preceding voluntary movement are modulated by the mode of movement selection. Exp. Brain Res., 1995, 103: 429-439). One cortical area that is likely to be involved in this modulation is the supplementary motor area (SMA). Recent attempts to elucidate the neural generators of the readiness potential using spatiotemporal dipole source analysis, however, failed to establish a significant SMA contribution to the readiness potential. This might be explained by a failure of the proposed analyses to discriminate between SMA and motor cortex contributions to the readiness potential. We applied a dipole source analysis approach that better separates these overlapping source activities. The resulting source model includes an SMA source generating pre-movement activity consistent with evidence from intracranial recordings in humans. The SMA source accounts almost completely for the modulation of the readiness potential by different modes of movement selection. On the basis of these results, the relation between scalp-recorded movement-related activity, intracranially recorded potentials, and findings from functional imaging studies of voluntary movement, appears more transparent than suggested by previous dipole source analyses of premovement potentials.

Adult↗

PubMed1996

Executive functions and disease characteristics in Parkinson's disease.

In the present study, we investigated the association of two executive functions with disease characteristics in Parkinson's disease (PD), especially with severity of motor symptoms. We operationalized two executive functions, viz. fluency and cognitive shifting, each in a number of tests with heterogeneous materials, but with an identical format. We calculated the correlations between test performance and disease characteristics, including the factor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). The results of this study show that only cognitive shifting was consistently associated with the severity of motor symptoms in PD, in particular with rigidity. None of the fluency tests had a significant association with severity of motor symptoms. The present study indicates that PD, as reflected by the severity of motor symptoms, is not associated with a general decrease in executive function. In spite of the fact that both are executive functions and both require generation of items, fluency and cognitive shifting are differentially related to PD.

Aging↗