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A R Cools

Publications and source records attributed to A R Cools.

At least 145 records · Page 8Linked to original sources
PubMed1993

The substantia innominata complex and the peripeduncular nucleus in orofacial dyskinesia: a pharmacological and anatomical study in cats.

It has been shown that orofacial dyskinesia, i.e. a syndrome of abnormal involuntary movements of the facial muscles, can be elicited from the sub-commissural part of the globus pallidus and the adjoining dorsal parts of the extended amygdala in cats. Until now it is unknown whether the peripeduncular nucleus, which receives input from these structures according to anterograde tracing studies, plays a role in the funneling of orofacial dyskinesia to lower output stations. In the present study the connection of the subcommissural part of the globus pallidus and dorsal parts of the extended amygdala with the peripeduncular nucleus was investigated anatomically, using cholera toxin subunit B as a retrograde tracer, and functionally, using intracerebral injections of GABAergic compounds. The anatomical data show that the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala were marked by cholera toxin sub-unit B-immunoreactive cells following injections of this retrograde tracer into the peripeduncular nucleus. Thus, it could be confirmed that the peripeduncular nucleus receives input from the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala. Still, the orofacial dyskinesia elicited by local injections of the GABA antagonist picrotoxin (500 ng/0.5 microliters) into the sub-commissural part of the globus pallidus and dorsal extended amygdala was only in part attenuated by local injections of the GABA agonist muscimol (100 ng/l microliters) into the peripeduncular nucleus. Only the number of tongue protrusions was significantly attenuated, but not that of the ear and cheek movements. Furthermore, tongue protrusions, but no additional oral movements, were elicited by picrotoxin injections (375-500 ng) into the peripeduncular nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Bimodal shape of individual variation in behavior of Wistar rats: the overall outcome of a fundamentally different make-up and reactivity of the brain, the endocrinological and the immunological system.

An overview of the most important features of the two distinct types of individuals which normally co-occur in an unselected population of Wistar rats is given. It reveals that the overall make-up and reactivity of the brain, as well as the endocrinological and immunological systems differ completely between the two types of individuals. Each of these types of individuals has its own individual-specific hardware and software to cope with challenges from the internal or external environment, requires its own optimal niche, and is vulnerable for its own set of stressors.

Animals↗
PubMed1992

Injections of the NMDA-antagonist D-2-amino-7-phosphonoheptanoic acid (AP-7) into the nucleus accumbens of rats enhance switching between cue-directed behaviours in a swimming test procedure.

The present study explores the behavioural effects of intra-accumbens injections of D-2-amino-7-phosphonoheptanoic acid (AP-7), a selective competitive N-methyl-D-aspartate (NMDA) receptor antagonist, using a swimming test procedure, in which rats were forced to swim for 6 min. The behaviour of the rats was analysed in terms of cue-directed (CDBs) and non-cue-directed behaviours (NCDBs). AP-7 (100-500 ng/0.5 microliter) dose-dependently enhanced the number of switches to CDBs, without affecting the number of switches to NCDBs. Further analysis of the data showed that the number of switches between CDBs was enhanced, while no effect was found on the number of switches from NCDBs to CDBs, from CDBs to NCDBs or between NCDBs. These data suggest that the NMDA-receptor in the nucleus accumbens is involved in the ability to switch between cue-directed behaviours.

2-Amino-5-phosphonovalerate↗
PubMed1992

Differences in spike-wave discharges in two rat selection lines characterized by opposite dopaminergic activities.

In the present study, 48 h electroencephalographic recordings were made in order to examine the incidence and duration of spike-wave discharges in apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) lines of an outbred strain of Wistar rats. In comparison with APO-UNSUS rats APO-SUS rats showed significantly more spike-wave discharges, especially during the dark period: both the mesor and the amplitude of the optimal cosine fitted to the data were significantly increased, whereas neither the acrophase nor the period length (24 h) differed. It is suggested that both the relatively low dopaminergic activity of the nigrostriatal fibres and the relatively high dopaminergic activity of the mesolimbic fibres, i.e. two well characterized features of the APO-SUS rats, significantly contribute to the high incidence of spike-wave discharges in these APO-SUS rats.

Animals↗
PubMed1992

Problem-solving behaviour in apomorphine-susceptible and unsusceptible rats.

Pharmacogenetically selected apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) rats were trained in a discrimination learning paradigm. After the initial discrimination task was solved, reinforcement contingencies were reversed. No differences between APO-SUS and APO-UNSUS animals were found in the rate of learning. However, negative transfer from the initial discrimination to its reversal was less for the APO-SUS rats than for the APO-UNSUS rats. Moreover, the APO-SUS rats responded more to the relevant dimension (light) than the APO-UNSUS rats in the last 100 trials before solving the initial problem as well as the reversal. During overtraining on the first problem, APO-SUS animals responded less to an irrelevant dimension (position of the lever) than APO-UNSUS animals. In the first 100 trials of the reversal APO-SUS rats responded more to another irrelevant dimension (noise) than APO-UNSUS rats. The data show that APO-SUS and APO-UNSUS rats used the various dimensions (visual, auditory, and spatial) differently in the chosen discrimination learning paradigm. It is concluded that the interline differences found are the consequences of the interline differences in the dopaminergic activity of the ventral and dorsal striatum.

Acoustic Stimulation↗
PubMed1992

Effects of haloperidol on the acquisition of a spatial learning task.

The effects of systemic injections of the dopaminergic antagonist haloperidol on the acquisition of the Morris water maze with either a visible or an invisible platform (nonspatial vs. spatial learning) were investigated. An open field test was used for selecting a dosage (< or = 0.1 mg/kg), that (hardly) affected locomotor behaviour. Differential effects were found. At 0.1 mg/kg, haloperidol reduced locomotion in the open field, impaired acquisition in the Morris maze with a visible platform, and blocked escape onto an invisible one. Even though 0.07 mg/kg haloperidol reduced locomotion, both 0.04 and 0.07 mg/kg only impaired Morris maze performance in the spatial version. A large effect was found in the first trial of every day's training block. These results indicate that haloperidol at low doses can lead to a moderate but significant impairment of spatial learning. It is suggested that the effects found are related to the function of the striatal areas in cue- and noncue-directed behaviour.

Animals↗
PubMed1992

Jaw muscle activity, the nucleus accumbens, and dopaminergic agonists: a new approach.

A method was developed to analyze electromyographic (EMG) signals in terms of power, viz., a measure for overall muscle activity, and number of seconds marked by distinct frequency ranges. With the help of this method, the effects of intraaccumbens administration of distilled water, the D1 receptor agonist SK&F 38393 (SKF; 5 micrograms), the D2 receptor agonist LY 171555 (LY; 10 micrograms), and their combination upon the EMG signals of the masseter and the digastric muscle were analysed in freely moving rats. Only the combined treatment affected the power: The noted increase was limited to the digastric muscle. The time/frequency analysis was limited to frequency ranges 3-4 Hz (class A), 4-5 and 5-6 Hz (class B), and 6-7, 7-8, ..., 12-13, and 13-14 Hz (class C). Apart from a small effect of SKF alone and of SKF in combination with LY on class B of the masseter muscle, neither SKF nor LY affected class A or B. SKF and LY increased and decreased, respectively, class C in both muscles. The data suggest that SKF and LY elicited both opposite and synergistic effects. The method is a new tool to analyze EMG signals in freely moving rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Interaction between aminergic systems in mesolimbic structures: the importance of 5-HT2, D2 and D1 receptors in the olfactory tubercle for the atypical profile of neuroleptics.

This study shows that the 5-HT2 antagonists ketanserin and ritanserin which on top of administration of classical neuroleptics reduces negative symptoms in schizophrenia as well as extrapyramidal side effects, are the most potent inhibitors of the dopamine-specific responses of the olfactory tubercle (OT); like atypical neuroleptics (2), they are far less effective when injected in the nucleus accumbens (ACC). We suggest that 5-HT2, D2 and/or D1 antagonism within the olfactory tubercle is necessary, but not sufficient for the atypical profile of neuroleptics.

Animals↗
PubMed1992

Corticosteroid receptor plasticity in the central nervous system of various rat models.

The action of corticosteroids in the central nervous system (CNS) is mediated by two distinct corticosteroid receptors: the mineralocorticoid and glucocorticoid receptors (MR and GR respectively). Using an established in vitro binding assay system, MR and GR binding parameters were determined in the hippocampal, hypothalamic and pituitary cytosol of various rat models. In the (pharmaco-)genetically selected rat lines, the apomorphine susceptible (APO-SUS) rats showed a significant increase in the hippocampal and pituitary MR binding capacities (but not affinity) compared to those in the apomorphine-unsusceptible (APO-UNSUS) rats. In immunologically-altered Lewis (LEW/N) rats and in spontaneously hypertensive rats (SHR), increased hippocampal MR capacity (but not affinity) and hypothalamic MR capacity were observed compared to their respective control, Wistar (WIST) and Wistar Kyoto (WKY) rats. In addition, compared to WKY rats, SHR rats also showed a much greater pituitary but lesser hypothalamic GR binding capacity. In rats subjected to alteration in environmental conditions, the long-term effects of a short inescapable stress resulted in a significant increase in both hippocampal MR and GR while the pituitary and hypothalamic MR and GR do not differ in the stress and control groups. In rats subjected to a defeat test, a decrease in hippocampal MR and GR was observed 3 weeks (but not 1 week) later.

Animals↗
PubMed1991

Dopamine D1 receptors in the sub-commissural part of the globus pallidus and their role in oro-facial dyskinesia in cats.

The possible role of dopamine D1 receptors in the sub-commissural part of the globus pallidus in the induction of oro-facial dyskinesia was studied in cats. The present study reveals two findings. Firstly, bilateral injections of the D1 agonist (+/-)-SK& F38393 into the ventral pallidal area elicited oro-facial dyskinesia, which was quantified in terms of numbers of tongue protrusions. The results show that the dose-effect curve was bell-shaped (1.0, 1.75, 2.5, 5.0 micrograms/0.5 microliters (+/-)-SK&F38393). The oro-facial dyskinesia elicited by (+/-)-SK&F38393 was highly comparable to the oro-facial dyskinesia elicited by injections of the GABA antagonist picrotoxin or the acetylcholine agonist carbachol into the sub-commissural part of the globus pallidus. Secondly, the inactive enantiomer of SK&F38393, i.e. S(-)-SK&F38393, was found to be ineffective in eliciting oro-facial dyskinesia when injected in a dose equivalent to 50% of the most effective dose of the racemic mixture of (+/-)-SK&F38393. Furthermore, the effect elicited by 2.5 micrograms/0.5 microliters (+/-)-SK&F38393 was significantly attenuated by local injection of the D1 antagonist R(+)-SCH23390 in a dose which had no effect itself (1.0 micrograms/0.5 microliters). These findings indicate that the effects elicited by (+/-)-SK&F38393 are D1-specific. The present results thus clearly indicate that dopamine D1 receptors within the sub-commissural part of the globus pallidus are involved in mediating oro-facial dyskinesia in cats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Functional interaction between dopamine D1 and D2 receptors in rat jaw movements.

The functional interaction between dopamine D1 and D2 receptors in dopamine-mediated jaw movements was studied in ketamine-anaesthetized rats after C1 spinal transection. Jaw movements were recorded by means of a light-emitting diode attached to the mandible; the method permits a detailed qualitative and quantitative analysis of jaw movements. D1 stimulation with SKF38393 (10 mg/kg i.v.) produced frequent bursts of teeth chattering, which were abolished by pretreatment with SCH23390 (0.25 mg/kg i.v.). D2 stimulation by quinpirole (1-10 mg/kg i.v.) produced infrequent bursts of jaw movements, which were characterized by low frequency jaw opening and closure movements from the rest position of the jaw, and absence of tongue protrusions. An additional stimulation of D1 receptors by giving SKF38393 30 min later produced an almost continuous pattern of jaw openings but less closure movements from the rest position, and the openings were accompanied by frequent tongue protrusions. These results clearly demonstrate that the type of oral behaviour produced by stimulation of D1 and D2 receptors together is qualitatively different from that produced by stimulation of either D1 or D2 receptors alone.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

The involvement of dopamine D1 and D2 receptors in the effects of the classical neuroleptic haloperidol and the atypical neuroleptic clozapine.

There is increasing evidence that classical neuroleptics (neuroleptics that induce so called extrapyramidal side effects) and atypical neuroleptic drugs (neuroleptics that do not induce these side effects) have different mechanisms of action. It has been suggested that atypical neuroleptics may work at least partially through the dopamine D1 receptor whereas classical neuroleptics are generally considered to work via the dopamine D2 receptor. In order to test this hypothesis we evaluated the role of D1 and D2 receptors in the effects of haloperidol and clozapine in the paw test. This test has been shown to be a good animal model for both the therapeutic efficacy of classical and atypical neuroleptics as well as for the extrapyramidal side effect potential of classical neuroleptics. The present results show that the effects of haloperidol in the paw test are antagonised by a dopamine D2 agonist but not by a D1 agonist, whereas the effects of clozapine are reversed by a D1 agonist but not by a D2 agonist. These data suggest that haloperidol produces its therapeutic and extrapyramidal side effects via blockade of dopamine D2 receptors, whereas clozapine produces its therapeutic effects via blockade of dopamine D1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Motor activity and the GABAA-receptor in the ventral pallidum/substantia innominata complex.

The present study deals with the role of the gamma-aminobutyric acid-A (GABAA) receptor in motor activity in the rostral part of the ventral pallidum/substantia innominata complex. Both the specific GABAA antagonist bicuculline (25-100 ng/0.5 microliter) and the GABAA agonist muscimol (25 ng/0.5 microliter) enhanced motor activity. It was moreover found that bicuculline (50-100 ng) dose-dependently attenuated the activity induced by muscimol (25 ng). Conversely, muscimol (25 ng) attenuated the bicuculline (25-50 ng) induced activity. These data thus show that both stimulation and blockade of GABAA receptors within the area under study enhance motor activity.

Animals↗
PubMed1991

Evidence that dopamine in the nucleus accumbens is involved in the ability of rats to switch to cue-directed behaviours.

Recently we have reported that injections of d-amphetamine into the nucleus accumbens enhanced the number of switches to cue-directed behaviours without an effect on the number of switches to non-cue-directed behaviours in a swimming test. In the present study we investigated to what extent this effect is mediated via the dopaminergic system in the nucleus accumbens. For that purpose drugs selective for D1- and D2-receptors were studied in this swimming test. It was found that the selective D2-agonist LY 171 555 (50 ng/0.5 microliters) enhanced the number of different cue-directed behaviours. The selective D2-antagonist raclopride (50 ng/0.5 microliters) decreased it. Furthermore an ineffective dose of raclopride attenuated the effect of LY 171 555. Both the selective D1-antagonist SCH 23390 (400 ng/0.5 microliters) and the selective D1-agonist SKF 38393 (50-400 ng/0.5 microliters) decreased the number of different cue-directed behaviours. The effect induced by SCH 23390 could not be blocked by SKF 38393. Similarly the effect induced by SKF could not be attenuated by SCH 23390. These data point to a role for dopamine D2-receptors in the ability to switch to cue-directed behaviours. The present findings do not yet allow the conclusion that D1-receptors are involved.

Animals↗
PubMed1991

Subregions of the caudate nucleus and their in- and output channels in oro-facial dyskinesia: a behavioural and retrograde tracing study in the cat.

Previous studies have shown that the feline caudate nucleus contains DPI-sensitive (caput nuclei caudati, anterodorsal part; r-CRM) and DPI-insensitive (caput nuclei caudati, rostromedial part; CRM) regions. Stimulation of dopamine receptors within the r-CRM by dopamine or DPI are known to elicit oro-facial dyskinesia (OFD), i.e. a syndrome of tic-like contractions of the facial muscles in combination with tongue protrusions. OFD is also elicited from the sub-commissural part of the globus pallidus (scGP), a first order output station of the r-CRM, but not from the CRM. On the basis of these data it has been hypothesized that (1) OFD is a specific feature of the r-CRM, but not the CRM; (2) effects elicited from the r-CRM are funneled via the scGP, and that (3) r-CRM and CRM are differentially innervated. Cats were bilaterally equipped with cannulas directed at the CRM or r-CRM and scGP. Following recovery from the operation the cats received bilateral injections of DPI into CRM (5 micrograms/5 microliter) or r-CRM (5 and 10 micrograms/5 microliter), the latter in combination with muscimol (50 and 100 ng/1 microliter) into the scGP or its solvent. Subsequently, behaviour was analyzed. OFD, quantified in number of tongue protrusions, was only elicited from the r-CRM, but not from the CRM confirming previously reported data in this respect. Furthermore the effect varied according to the dose used. The OFD elicited from the r-CRM was found to be blocked at the level of the scGP by local injections of muscimol, a GABA agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Efferent connections of the striatopallidal and amygdaloid components of the substantia innominata in the cat: projections to the nucleus accumbens and caudate nucleus.

Enkephalin immunoreactivity is used to divide the feline substantia innominata into circumscript subregions, i.e. the "striatopallidal system" and the "extended amygdala". In addition, enkephalin immunoreactivity is used to subdivide the striatopallidal system into two distinct areas, i.e. the subcommissural part of the globus pallidus displaying high enkephalin immunoreactivity and the ventral pallidum displaying moderate enkephalin immunoreactivity. The anterograde axonal transport of Phaseolus vulgaris-leucoagglutinin is used to study the efferents of these areas innervating the caudate nucleus and the nucleus accumbens. It is found that the enkephalin-immunoreactive subcommissural part of the globus pallidus as well as the dorsal enkephalin-immunoreactive regions of the extended amygdala project topographically along a rostrocaudal and mediolateral dimension to the nucleus accumbens. The far rostral parts of the caudate nucleus are found to be innervated by the subcommissural part of the globus pallidus whereas the extended amygdala has no such connection. This pathway is also found to be topographically organized along a mediolateral dimension. The non-enkephalin-immunoreactive area ventral and lateral to the subcommissural part of the globus pallidus is found to have no projections to the nucleus accumbens and caudate nucleus. This region rather innervates the olfactory tubercle. In contrast to the striatopallidal system the sublenticular part of the extended amygdala preferentially projects to the adjoining part of the extended amygdala, i.e. the bed nucleus of the stria terminalis. However, the ventral regions preferentially innervate the medial division of the bed nucleus of the stria terminalis whereas the dorsal regions preferentially innervate the lateral division of the bed nucleus of the stria terminalis. These data indicate that the differential forebrain systems represented in the feline substantia innominata, i.e. the striatopallidal system and extended amygdala have differential output stations. The results are discussed in view of the role of the subcommissural part of the globus pallidus and the nucleus accumbens in orofacial dyskinesia and schizophrenia, respectively.

Amygdala↗
PubMed1991

Differential role of mineralocorticoid and glucocorticoid receptors in the genesis of dexamphetamine-induced sensitization of mesolimbic, alpha 1 adrenergic receptors in the ventral striatum.

The present study was carried out to investigate the role of corticosteroids in the dexamphetamine-induced sensitization of the mesolimbic, noradrenergic system. The experimental design of adrenalectomy and hormone replacement was chosen for exploration of this question. The dexamphetamine-induced sensitization of mesolimbic, alpha 1 adrenergic receptors in the ventral striatum was studied by administering intra-accumbens injections of the alpha 1 agonist, phenylephrine (10 micrograms), given 24 h after a priming injection of intra-accumbens administered dexamphetamine (10 micrograms), which itself elicits an increase in locomotor activity. In this paradigm phenylephrine produces an increase in locomotor activity, an effect which does not occur in rats which are not sensitized by dexamphetamine. Adrenalectomy produced a slight, but significant, attenuation of the response to the priming injections of dexamphetamine. Replacement treatments (500 micrograms/kg per drug) with corticosterone or deoxycorticosterone, agents which preferentially bind with mineralocorticoid receptors, did not affect the dexamphetamine response, whereas replacement treatment with dexamethasone, which preferentially binds with glucocorticoid receptors, strongly potentiated this response. In view of the fact that the adrenalectomy-induced fall in corticosteroids can produce an up-regulation of glucocorticoid receptors, but not mineralocorticoid receptors, these data led to the conclusion that glucocorticoid receptors which are present in the cell bodies of noradrenergic, serotonergic and dopaminergic neurons are critical for the dexamphetamine response in drug-naive rats. The phenylephrine response was also strongly enhanced in adrenalectomized rats treated with dexamethasone. Since the magnitude of the dexamphetamine response is known to determine the magnitude of the phenylephrine response, the role of glucocorticoid receptors in the dexamphetamine-induced sensitization of the phenylephrine response remains to be established. Conversely, adrenalectomy nearly completely abolished the dexamphetamine-induced sensitization of the phenylephrine response. The latter response was reinstated by replacement treatment with corticosterone or deoxycorticosterone. These data show that mineralocorticoid receptors, which are present among others in the ventral striatum, are critical for the dexamphetamine-induced sensitization of mesolimbic, alpha 1 adrenergic receptors in the ventral striatum. The present study opens the perspective that secretion of corticosteroids in response to stressful stimuli--be it pharmacological or environmental--is the key to the question of why dexamphetamine and environmental challenges are interchangeable in the development of sensitization of mesolimbic, alpha 1 adrenergic receptors.

Adrenalectomy↗