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A R Cools

Publications and source records attributed to A R Cools.

At least 163 records · Page 9Linked to original sources
PubMed1991

Role of the nucleus accumbens in social memory in rats.

Recognition of a juvenile conspecific by an adult male rat is known to be reflected by reduced anogenital investigation (A.G.I.) of this young individual by the adult, when the two animals are reexposed to each other after some short delay. As the delay is increased, the reduction in A.G.I. is reduced. This measure of social memory can be modulated by several drugs, among others cholinomimetic agents. In this study, the effects of direct manipulation of the nucleus accumbens were studied. Local administration of (3,4-dihydroxyphenylimino)-2-imidazoline (DPI: 0.1-1.5 micrograms) decreased investigatory behaviour at the second exposure after a long interexposure-interval, while ergometrine (0.1 micrograms) counteracted this reduction by DPI. These findings suggest a role for the nucleus accumbens in social recognition, in particular for the so-called DAi receptors which are stimulated and inhibited by DPI and ergometrine respectively.

Animals↗
PubMed1991

Role of neostriatum and nucleus accumbens in stepping induced by apomorphine and dexamphetamine.

Systemic administration of apomorphine and dexamphetamine are known to produce circling in rats by changing the functioning of hindlimb stepping and forelimb stepping, respectively. In the present study intracranial injections of the dopamine antagonist sulpiride were used to study the involvement of the neostriatum and nucleus accumbens in these effects. It was found that injections of sulpiride into the neostriatum, but not the nucleus accumbens, dose-dependently (1-20 ng) reduced the number of apomorphine-induced hindlimb doublets without affecting the dexamphetamine-induced forelimb crossing steps. On the other hand, it was found that injections into the nucleus accumbens, but not the neostriatum, reduced the number of dexamphetamine-induced forelimb crossing steps without affecting the apomorphine-induced hindlimb doublets. This effect was not dose-dependent. The data suggest that the neostriatum, but not the nucleus accumbens, is primarily involved in the apomorphine-induced changes in hindlimb stepping, and that the nucleus accumbens, but not the neostriatum, is primarily involved in the dexamphetamine-induced changes in forelimb stepping.

Animals↗
PubMed1990

Enhancement in switching motor patterns following local application of the glutamate agonist AMPA into the cat caudate nucleus.

The effect of caudate nucleus (CN)-injections of the glutamate agonist DL-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), viz. an agonist of quisqualate receptors, on switching behaviour was investigated: first, cats had to switch from hanging with the forepaws on the bar to climbing on the bar; then, they had to switch to walking; finally, they had to switch to jumping off the bar. AMPA induced limb deficits, i.e. unilateral incorrect or absent placing of the fore- and/or hindlimb, in part of the tested cats; in the remainder of the tested animals AMPA reduced climbing time. Limb deficits were prevented by the broad-spectrum glutamate antagonist kynurenic acid (KYN) and by the selective NMDA antagonist D-2-amino-7-phosphono-heptanoate. In all cats AMPA increased the number of head movements as well as that of walking-restarts. These effects were counteracted only by KYN. These data show that part of the AMPA-induced effects were selectively mediated by quisqualate receptors. The present data are discussed in view of the role of the caudate nucleus in switching behaviour.

Animals↗
PubMed1990

Effects of intrastriatal apomorphine on changes in switching behaviour induced by the glutamate agonist AMPA injected into the cat caudate nucleus.

Bilateral intracaudate application of the glutamate agonist DL-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), viz. an agonist of quisqualate receptors, is known to produce the following effects in cats that had to climb on a small wooden bar and, subsequently, to switch to distinct patterns: it produces increases in switching from one pattern to another pattern (1) and it induces limb deficits, i.e. unilateral deficient placing of the fore- and/or hindlimb. In the present study, the effect of stimulating striatal dopamine receptors on behavioural changes induced by intracaudate injections of AMPA was investigated. Therefore, the dopamine agonist apomorphine was injected into the caudate nucleus 5 min before the striatal injection of 1.0 micrograms AMPA. AMPA-induced increases in switching behaviour were prevented by 0.6 micrograms, but not 0.3 micrograms, apomorphine. In contrast, AMPA-induced limb deficits were not prevented by pretreatment of apomorphine. In view of the notion that the dopaminergic caudate nucleus, its output station the substantia nigra, pars reticulata and the nigral output station the deeper layers of the colliculus superior are essential for switching behaviour, but not for the display of disturbances like AMPA-induced limb deficits, the present data strongly suggest that only AMPA-induced changes in switching, but not AMPA-induced limb deficits, are mediated by the caudato-nigro-collicular circuitry. The glutamate receptor-selectivity of the modulatory action of dopamine is discussed.

Afferent Pathways↗
PubMed1990

Behavioral correlates of a progressive dysfunctioning of the deeper layers of the colliculus superior: effects of picrotoxin.

Intracaudate injections of relatively high doses of apomorphine produce a regression in motor behavior of cats collecting food pellets in a treadmill design (25). It has been hypothesized that this regression is partly due to functional disturbances in brain regions receiving (in) directly striatal output signals. In view of this hypothesis it was investigated whether experimentally induced changes in GABAergic activity within the deeper layers of the colliculus superior, which is a second order output station of the caudate nucleus, are also able to elicit a regression in motor behavior. Therefore, motor behavior of cats was tested in the treadmill paradigm before and after intracollicular injections of the GABA antagonist picrotoxin. Picrotoxin produced dose-dependently a regression in motor behavior which was comparable to that elicited by intrastriatally injected apomorphine. The noted effects were GABA-specific since muscimol attenuated the picrotoxin-induced regression. The present data are discussed in view of a model for a hierarchical organization of the brain.

Animals↗
PubMed1990

Local as well as remote functional and metabolic changes after focal ischemia in cats.

Behavior and limb placing ability were analyzed acutely and subacutely (up to 21 days) following unilateral occlusion of the middle cerebral artery (MCA) in cats. Immediately following occlusion, all tested cats started to display a sequence of different behaviors, characteristic for 1) an ipsilateral inhibition of dopaminergic activity in the caudate nucleus (CN); 2) an inhibition of GABAergic activity in the reticular substantia nigra (SNR); 3) a stimulation of GABA receptors in the deeper layers of the colliculus superior (CSDL) (starting-time of these phases: about 4, 12 and 25 min, respectively). The latter behavior was also present subacutely. In addition, unilateral orofacial dyskinetic movements were observed acutely as well as subacutely. Contralateral limb placing was deficient in all cats 60 min postocclusion; it was at least partly restored subacutely. Twenty-one days after the occlusion, [14C]-2-D-deoxyglucose uptake was relatively reduced in the ipsilateral CN (especially in its posterior part), the ipsilateral SNR and the ipsilateral CSDL. The anterior CN appeared to be less affected than the posterior CN. Metabolism was relatively reduced in the sensorimotor cortex only in part of the tested cats. The data show that unilateral MCA occlusion produces consistent functional changes in all structures studied apart from the sensorimotor cortex, viz. the CN, the SNR and the CSDL.

Animals↗
PubMed1990

Search after neurobiological profile of individual-specific features of Wistar rats.

The first part of this study demonstrates that the bimodal shape of variation in "fleeing" and "nonfleeing" or "freezing" rats of an outbred strain of Wistar rats forms part of an overall biomodal variation in behavioural responses to injections of agents, which selectively alter, or reflect, the noradrenergic or dopaminergic activity in the ventral striatum, and dopaminergic activity in the dorsal striatum, the GABA-ergic activity in the substantia nigra, pars reticulata, and the GABA-ergic activity in the deeper layers of the superior colliculus. It is concluded that the "fleeing" and "nonfleeing" rats, each of them marked by their own trans-situational consistency in pharmacological and behavioural responses, represent the two fundamentally different types of individuals which normally exist in unselected populations of rodents. The second part of this study demonstrates that the pharmacogenetic selection of apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) rats, i.e., one individual-specific feature of the overall bimodal variation for pharmacological responses in our outbred strain of rats, is a valid tool to disperse the above-mentioned individual-specific features as far as possible. First, these lines allowed us to prove that the overall bimodal shape of variation in pharmacological and behavioral responses of individual outbred rats is in part genetically determined. Second, these lines allowed us to prove that a bimodal variation in neurochemical features of the circuitry, in which the ventral striatum is embedded, underlies the overall bimodal variation in pharmacological and behavioural responses. Third, these lines allowed us to demonstrate that a fundamental difference in organizing behaviour with the help of external and internal information has to be considered as a common factor giving rise to the individual differentiation found in the present study. Given the notion that this individual differentiation appears to be valid across lines, substrains and strains of rats, the present study lays the foundation for understanding at least a part of the physiological basis underlying differences between the two fundamentally different types of individuals existing in normal populations of rodents.

Animals↗
PubMed1990

Bimanual simultaneous motor performance and impaired ability to shift attention in Parkinson's disease.

The ability to share time and to shift attention between bimanual simultaneous motor tasks were studied in 18 patients with Parkinson's disease (PD) and 19 age- and intelligence-matched controls. The task consisted of drawing triangles with the dominant hand and squeezing a rubber bulb with the nondominant hand. Motor performance was measured using the variables: amplitude of squeezing, frequency of squeezing and velocity of drawing triangles. After eliminating variance due to baseline differences in single-handed performance, the bimanual simultaneous performance of PD and controls turned out to be similar to the frequency of squeezing and the velocity of drawing triangles. The amplitude of squeezing, however, differed between the two groups: it was significantly reduced in PD. Arguably the disturbance in the bimanual performance of PD patients was not due to a disorder of time sharing, but to a decreased ability to shift attention from the visually cued task to the non visually cued task. The results agree with current evidence that PD patients are more impaired when they have to rely upon internal control for the regulation of shifting attention than when external cues are available.

Aged↗
PubMed1989

Involvement of the substantia innominata/ventral pallidum complex in transmitting forelimb muscular rigidity evoked from the nucleus accumbens in rats.

In the present study it was investigated whether muscular rigidity elicited from the nucleus accumbens could be transmitted via the substantia innominata/ventral pallidum (SI/VP) complex. For this purpose rats were equipped with cannulae aimed at the nucleus accumbens and/or the SI/VP, and with electrodes in the triceps muscle of the forelimb. In the first set of experiments it was found that the GABA agonist muscimol (10-25 ng/0.5 microliters) dose-dependently increased tonic EMG activity upon injection into the SI/VP region. The GABA antagonist bicuculline (50 ng/0.5 microliters) antagonized the effects of muscimol (25 ng/0.5 microliters). In the second set of experiments it appeared that the increase in tonic EMG activity induced by haloperidol (1000 ng/0.5 microliters) injected into the nucleus accumbens was antagonized by subsequent injection of bicuculline (25 ng/0.5 microliters) into the SI/VP complex. These data suggest that the SI/VP complex may be one station through which the muscular rigidity elicited from the nucleus accumbens is transmitted to lower brain structures.

Animals↗
PubMed1989

Evidence that apomorphine and (+)-amphetamine produce different types of circling in rats.

Apomorphine and (+)-amphetamine are known to produce circling in naive rats. Frame by frame analysis of videotape recordings of the behaviour of Wistar rats treated with a subcutaneous injection of apomorphine (1.1 mg/kg; n = 8) or (+)-amphetamine (0.5 and 1.0 mg/kg; n = 8 and n = 8) was used to study this behaviour in more detail. In line with previously reported studies, apomorphine was found to change the functioning of hindlimb stepping. In contrast, (+)-amphetamine was found to change the functioning of forelimb stepping. These data imply that apomorphine and (+)-amphetamine produce their drug-specific circling via different substrates within the brain.

Amphetamine↗
PubMed1989

Oro-facial dyskinesia and the sub-commissural part of the globus pallidus in the cat: role of acetylcholine and its interaction with GABA.

The possible role of cholinergic mechanisms in the sub-commissural part of the globus pallidus (scGP) in the induction of oro-facial dyskinesia (OFD) was studied in cats. Local injections of the cholinergic agonist carbachol into the scGP elicited tongue protrusions in a dose dependent way (100-1000 ng/0.5 microliters). The effect elicited by 1000 ng carbachol was selectively antagonized by the cholinergic antagonist scopolamine (10 micrograms/0.5 microliters); this dose of scopolamine was ineffective when injected alone. The tongue protrusions resulted from both normal and abnormal movements: whereas normal movements simply consisted of protruding the flat tongue, abnormal movements implied a variety of movements, especially curling upwards the lateral side(s) or tip of the tongue inside or outside the oral cavity. The abnormal carbachol-induced tongue protrusions formed part of a syndrome marked by dyskinetic movements of the muscles of the eye, ear and cheek, and were identical to those seen previously after local injections of picrotoxin (250-500 ng). Intra-pallidal injections of the abovementioned dose of scopolamine had no effect on the tongue protrusions induced by local injections of 375 ng picrotoxin. However, local injections of 100 ng muscimol, which was previously found to attenuate significantly the effect of 375 ng picrotoxin and which was ineffective when injected alone, significantly attenuated the tongue protrusions induced by local injections of 1000 ng carbachol. These data suggest that the cholinergic effects are mediated via a GABAergic mechanism, but not vice versa. The results are discussed in view of GABAergic and anti-cholinergic therapies used in oro-facial dyskinesia.

Acetylcholine↗
PubMed1989

The involvement of the nucleus accumbens in the ability of rats to switch to cue-directed behaviours.

Previous studies have shown that the dorsal striatum is involved in switching arbitrarily behaviour (switching to non cue-directed behaviours). These experiments also revealed that switching behaviour with the help of currently available sensory information (switching to cue-directed behaviours) was not influenced when striatal function was blocked. A number of studies suggested that the nucleus accumbens could mediate the latter type of switching. For testing this hypothesis we used the swimming-test as it allows for studying separately both cue-directed and non cue-directed behaviours. Rats with cannulae aimed at the nucleus accumbens were forced to swim after injection of distilled water (AD) or d-amphetamine (1-10 micrograms/0.5 microliter) in a circular water-tank from which there was no escape. Their behaviour was recorded and analysed according to the presence of cue-directed and non cue-directed behaviours. After six minutes a rope was introduced into the water-tank to determine whether the rats were able to change their behaviour with the help of this external stimulus as well. Rats treated with d-amphetamine showed an enhanced ability to switch to cue-directed behaviours in comparison with rats treated with AD. There was no effect on the ability to switch to non cue-directed behaviours. Furthermore there was a dose-dependent increase in the ability to escape along the rope. The results are taken as evidence that the nucleus accumbens is involved in switching to cue-directed behaviours.

Amphetamine↗
PubMed1989

Haloperidol and cognitive shifting.

In this study haloperidol appeared to affect the performance on a selected category of cognitive tasks considered to represent shifting aptitude. A pretest--post-test design was used with two groups of subjects: 17 patients suffering from idiopathic spasmodic torticollis, and 17 controls who were matched for age and intelligence. The results are discussed in relation to previous findings on haloperidol and cognition, shifting disorder in Parkinson's disease and changes in behavioural organization found in animals with an experimentally induced dopaminergic hypoactivity.

Attention↗
PubMed1989

Progressive pathology of the caudate nucleus, the substantia nigra pars reticulata and the deeper layers of the colliculus superior: acute behavioural and metabolic effects of intrastriatal kainic acid.

The acute behavioural and metabolic consequences of functional changes following unilateral intracaudate kainic acid at the level of the feline caudate nucleus, the substantia nigra pars reticulata and the deeper layers of the colliculus superior were investigated. The present study became possible since it was previously found that unilateral changes in neurotransmission processes in these structures all result in behavioural alterations that can be distinguished from each other. During the first 17 min after kainic acid, all animals displayed contralateral forced staccato head turning; these movements are characteristic for an activation of dopamine receptors and/or inhibition of GABA receptors in the rostromedial caudate nucleus. Between 15 and 50 min, all animals displayed fast, uninterrupted contralateral forced head, torso or body turning; these movements are characteristic for an activation of nigral GABA receptors. From about 48 min, all animals displayed sequences of short contralateral forced ear, head, torso and body turnings; these movements are characteristic for an inhibition of collicular GABA receptors. Furthermore, most cats displayed ipsilateral orofacial dyskinetic movements during the whole 180 min observation period. Metabolism was analysed in three cats that received [14C]2-D-deoxyglucose immediately before, 5 min after, or 70 min after kainic acid. Metabolism was increased in the ipsilateral caudate nucleus; this effect was most pronounced in the cat that received deoxyglucose immediately before kainic acid. Metabolic activity was increased in the ipsilateral substantia nigra pars reticulata; this effect was most pronounced in the cat treated with deoxyglucose 5 min after kainic acid. Metabolism was increased in the ipsilateral deeper layers of the colliculus superior in the cat that received deoxyglucose 70 min after kainic acid. The present behavioural and metabolic data suggest that kainic acid produces an increasing pathology resulting successively in functional changes in the caudate nucleus, its output-station the substantia nigra pars reticulata and the nigral output-station the deeper layers of the colliculus superior. It is suggested that the successive appearance of the latter effects is inherent in the hierarchical order of the brain structures under study. The occurrence of orofacial dyskinetic movements during the whole observation period suggests that the former movements were not mediated via the striato-nigro-collicular pathway. Finally, apomorphine injected in the ipsilateral caudate nucleus 1 week after kainic acid was significantly less effective compared to apomorphine injected 1 week before kainic acid. The c

Animals↗
PubMed1989

Anatomically distinct output channels of the caudate nucleus and orofacial dyskinesia: critical role of the subcommissural part of the globus pallidus in oral dyskinesia.

The findings in this feline study indicate that the enkephalin-positive subcommissural part of the globus pallidus, which is known to contain GABA and cholinergic cells projecting to the cortex, is innervated by the anterodorsal region of the caudate nucleus, but not by the core. Like stimulation of a particular subclass of dopamine receptors in the anterodorsal region of the caudate nucleus, inhibition of the GABA receptors in the noted part of the globus pallidus resulted in orofacial dyskinesia, viz. tic-like contractions of the facial, eye and ear muscles, and tongue protrusions. This phenomenon was elicited by intrapallidal injections of the GABA antagonist picrotoxin in a dose-dependent manner and could be attenuated by the GABA agonist muscimol. Previous studies have already shown that neither stimulation of the dopamine receptors in the core of the caudate nucleus nor any manipulation with the first- and second-order output-stations of the latter brain region, viz. (a) those regions of the substantia nigra, pars reticulata which receive afferents from the caudate nucleus, and (b) those regions of the intermediate layers of the superior colliculus which receive afferents from the latter nigral region, ever resulted in orofacial dyskinesia. These findings support the hypothesis that the anatomically distinct input-output channels of the caudate nucleus are differentially involved in orofacial dyskinesia. The clinical impact of these findings is discussed in view of the L-3,4-dihydroxyphenylalanine-induced tardive dyskinesia in man. In addition, the relevance of the anatomical data is discussed in view of the co-occurrence of Parkinson's Disease and Dementia of Alzheimer-type in certain patients.

Animals↗