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Biomedical subjects

A R Cools

Publications and source records attributed to A R Cools.

At least 199 records · Page 11Linked to original sources
PubMed1986

Mesolimbic dopamine and its control of locomotor activity in rats: differences in pharmacology and light/dark periodicity between the olfactory tubercle and the nucleus accumbens.

To compare the functions of the lateral olfactory tubercle (OT) and the medial nucleus accumbens (ACC), dopamine (DA), (3,4-dihydroxyphenylimino)-2-imidazoline (DPI), and ergometrine were injected into the brain of rats familiarized with the experimental cage in which locomotor activity was assessed. In all tests a volume of 0.5 microliter per side was used. Both DA (1-10 micrograms) and apomorphine (1-10 micrograms) increased locomotor activity when injected into the OT; similar injections into the ACC produced inconsistent effects. The OT effects were short-lasting, dose-dependent and antagonized by haloperidol (0.5-2.5 micrograms) in a dose-dependent manner. DPI (1-10 micrograms) too produced an increase when injected into the OT; this response was long-lasting, dose-dependent and potentiated by ergometrine (0.1-1.0 microgram). Ergometrine (0.1-1.0 microgram) dose-dependently increased activity over a period of 200 min in ACC and OT rats, although the response in OT rats was much smaller than that in ACC rats. Only the ergometrine response in ACC rats was dose-dependently suppressed by DPI (1-10 micrograms). ACC rats tested during the light period showed a weak stimulatory response to ergometrine in comparison with ACC rats tested during the dark period; OT rats showed reversed light/dark periodicity. Thus, OT rats significantly differed from ACC rats with respect to locomotor responses to dopaminergic agents, their pharmacological profile and their light/dark periodicity. Evidence is provided that the lateral tuberculum, but not the medial accumbens, is responsible for the stimulatory effect of dopamine and related compounds.

Animals↗
PubMed1986

GABAergic neurotransmission within the reticular part of the substantia nigra (SNR): role for switching motor patterns and performance of movements.

In order to investigate the role of GABAergic neurotransmission within the reticular part of substantia nigra (SNR) in the switching of motor patterns and the performance of movements, cats trained to walk on the running belt of a treadmill at constant speed were subjected to three different tests: a food dispenser test measuring the animals' capacity to switch motor patterns in order to get access to food during walking; an obstacle test measuring the animals' capacity to switch motor patterns in reaction to incoming obstacles; EMG recording of two representative antagonistic muscles of the hindlimb during walking on the treadmill. Local injection of a moderate dose of the GABA antagonist picrotoxin (PTX; 250-500 ng/0.5 microliter) into the SNR disrupted the animals' capacity to switch motor patterns in the food dispenser test, but not in the obstacle test. These animals displayed normal EMG patterns during walking. Higher doses of intranigral injections of PTX, however, impaired the execution of movements per se as detected by an increased number of 'faults' in the obstacle test and pathological EMG patterns during walking. These experiments support the view that the SNR plays a distinct role for switching motor patterns; the SNR is involved in the control of movements per se; the degree of motor disorder depends on the degree of pathology within this brain structure.

Animals↗
PubMed1986

The periaqueductal gray: a prerequisite for ACTH-induced excessive grooming.

The periaqueductal gray is known to be involved in the expression of a variety of behaviours such as aggression, beta-endorphin-induced immobility and peptide-induced excessive grooming. In order to establish whether the periaqueductal gray (PAG) is indispensible for peptide-induced excessive grooming, lesions were placed in the dorsal part of this structure. Subsequently, the grooming-inducing abilities of adrenocorticotropin (ACTH), beta-endorphin and bombesin were tested. The lesioned animals did not display excessive grooming after intracerebroventricular injection of ACTH. beta-Endorphin administration into the lesioned animals resulted in an extreme display of immobility. Local injection of bombesin into the PAG resulted in reduced scratching behaviour followed by immobility. It was hypothesized that excessive grooming (elicited by ACTH) may be mediated through a non-opioid primary target site-situated in the lesioned region of the PAG-while excessive scratching and immobility (elicited by bombesin or beta-endorphin, respectively) may be mediated through an opioid primary target site (situated in the remaining part of the PAG). Furthermore, the analysis of social behaviour of lesioned animals revealed that these animals reacted towards an unfamiliar partner predominantly with freezing behaviour. The increase of beta-endorphin-induced immobility and socially induced freezing (which is morphologically very similar to beta-endorphin-induced immobility) in lesioned animals supports the hypothesis that the release of opioid peptides such as beta-endorphin in the PAG plays a role in the regulation of social behaviour.

Adrenocorticotropic Hormone↗
PubMed1985

Typical and atypical antidepressant drug effects on locomotor activity after intra-accumbens injections in the rat.

Changes in spontaneous or drug-induced locomotor activity in rats were studied after injection of antidepressants in the nucleus accumbens. Antidepressant drugs, either alone or in combination with ergometrine, were injected bilaterally via fixed guide cannulas into the nucleus accumbens and locomotor activity was recorded during a period of 5 h. The after-effect, a long-lasting change in ergometrine-induced locomotor activity after priming with an antidepressant drug was also studied. It was concluded that: (a) The nucleus accumbens is a target site for antidepressant drugs in the rat. (b) Antidepressant drugs with mainly dopaminergic, noradrenergic or serotonergic features each show different effects in the test battery. (c) Typical as well as atypical antidepressants show common features.

Animals↗
PubMed1985

Further evidence for the role of the caudate nucleus in programming motor and nonmotor behavior in Java monkeys.

This study describes the short-term effects of intracaudate microinjections of carbachol in temporarily isolated and restrained Java monkeys. The monkeys were found to display a series of motor disturbances including blepharoptosis, facial twitches, tongue protrusions, ear flattening, torticollis, and compulsive alternations of rapid flexions and extensions of the extremities. In general, carbachol was found to produce consistent effects as far as it concerns its ability to elicit motor disturbances. Three of the five tested monkeys had previously received another series of carbachol injections when they were freely moving and living in a stabilized social group. Accordingly, the present study enabled us to compare the effectiveness of threshold doses of carbachol in the same monkey in two distinct situations. We concluded first, that motor disturbances and disturbances in social communication were closely coupled in relation to the involvement of a particular cholinoceptive substrate within the caudate nucleus of Java monkeys. Second, the motor disturbances under study appeared to require a larger degree of dysfunctioning of this substrate than did subtle disturbances in the social communication of these monkeys. And, finally, stress inherent to restraint increased the susceptibility of the cholinoceptive substrate within the caudate nucleus. The clinical impact of our findings is discussed in view of differences between the premorbid and manifest phases of Parkinson's disease.

Animal Communication↗
PubMed1985

Morphine and specific changes in the sensitivity of noradrenergic receptors within the "limbic" part of the feline caudate nucleus: a behaviour study.

The present study describes the behaviour effects of intracerebral injections of the noradrenergic (NE) agonist oxymetazoline and the NE antagonist phentolamine into the "limbic" part of the caudate nucleus of cats primed 24 hr earlier and/or treated acutely with morphine (5 mg/kg, IP). Drug-induced changes in the morphine-specific behaviour served as dependent variables. Experiments were performed during two different periods of the year, each of them marked by a characteristic sensitivity of alpha-like NE receptors to NE agents, viz. the so-called NE "antagonist" period during which the NE receptors were sensitive to the NE antagonist phentolamine and the so-called NE "agonist" period during which the NE receptors were sensitive to NE and the NE agonist oxymetazoline. The present study demonstrates that morphine reversed the initial sensitivity to oxymetazoline respectively insensitivity to phentolamine in animals tested in the NE "agonist" period. In animals tested in the NE "antagonist" period morphine did not reverse the initial insensitivity to oxymetazoline resp. sensitivity to phentolamine. Furthermore, evidence is provided that the initial sensitivity to NE agents did not conspicuously determine the animal's response to the acute administration of morphine. The data are discussed in view of the concept that the firing rate of NE fibres determines the actual sensitivity of presynaptic and postsynaptic NE receptors to NE agonists and antagonists.

Animals↗
PubMed1984

The striato-nigro-collicular pathway and explosive running behaviour: functional interaction between neostriatal dopamine and collicular GABA.

The nature of the functional interaction between neostriatal dopamine activity and collicular GABA activity was studied. To this end we analyzed the ability of apomorphine injections into the neostriatum (50-500 ng/0.5 microliters per side) to reinitiate explosive running behaviour in rats pretreated with a subthreshold dose of picrotoxin into the colliculus superior (30-80 ng/0.5 microliters per side). Apomorphine was found to reinitiate the former behaviour dose dependently and its effect could be antagonized by a very low dose of neostriatally applied haloperidol (250 ng/0.5 microliters per side). It was possible to delineate the most critical region within the structures studied. Evidence is presented in favour of the previously reported hypothesis that increasing dopaminergic neostriatal activity within the terminal region of the nitrostriatal pathway results in a decreasing GABAergic activity within the terminal region of the GABAergic striato-nigro-collicular pathway.

Animals↗
PubMed1984

Caudate nucleus and programming behaviour in cats: role of dopamine in switching motor patterns.

Cats were trained to walk on a specially designed treadmill: the cats were able to collect food pellets by switching motor patterns with or without the help of exteroceptive stimuli inherent to the treadmill. To study the involvement of the caudate nucleus in switching motor patterns cats received intracaudate bilateral injections of haloperidol. In addition, in a final series of experiments, EMG recordings of two antagonistic muscles, together with recordings of characteristic changes in the length of one muscle, were made before and after the haloperidol treatment. Haloperidol treatment resulted in a decreased number of motor patterns which were not directed by exteroceptive stimuli (non-exteroceptively directed motor patterns). This haloperidol-induced effect was dose-dependently counteracted by the additional intracaudate injections of apomorphine which per se remained ineffective. Haloperidol neither altered the number of food collecting attempts nor reduced the number of exteroceptively directed motor patterns. Furthermore, haloperidol did not affect the capacity to switch to proprioceptively directed motor patterns. Finally, haloperidol did not produce abnormalities in EMG and length signals recorded from hindlimb muscles. It is concluded that haloperidol selectively reduced the animal's capacity to 'programme non-stimulus directed motor behaviour'. The data are discussed in view of their significance for therapy of patients with basal ganglia disorders, such as patients suffering from Parkinson's disease.

Animals↗
PubMed1984

Basal ganglia and Parkinson's disease: neurobiological and pharmacological aspects in animals and man.

In this article, the neuroanatomy, neurochemistry and neurobiology of the nigrostriatal and mesolimbic circuitries of animals and man will be reviewed in order to gain insight into the pathognomy and etiology of cognitive and motor disorders in patients with Parkinson's disease, to increase insight into the mechanism of action of present-day antiparkinson agents, and to open perspectives for the design and development of new antiparkinson agents on a rational basis.

Acetylcholine↗
PubMed1984

Cognitive and motor shifting aptitude disorder in Parkinson's disease.

Eighteen patients suffering from Parkinson's disease and nineteen control subjects, who were matched for age and intelligence, were compared in tests measuring "shifting aptitude" at cognitive and motor levels (word production, sorting blocks or animals, and finger pushing sequences). It was found that Parkinson patients produced fewer different names of animals and professions in one minute than control subjects, needed more trials for detecting a shift in a sorting criterion, and produced fewer finger responses in a change of pushing sequence than control subjects. These results are interpreted as reflecting a central programming deficit that manifests itself in verbal, figural and motor modalities, that is, a diminished "shifting aptitude" characteristic of patients with dysfunctioning basal ganglia. The results are discussed in relation to changes of behaviour organisations in animals with dysfunctioning basal ganglia.

Aged↗
PubMed1983

Picrotoxin microinjections into the brain: a model of abrupt withdrawal 'jumping' behaviour in rats not exposed to any opiate?

Picrotoxin microinjections (0.5 microliter per side) given into the locus coeruleus, superior colliculus and central grey of freely moving Wistar rats produced an accelerating galloping locomotion, most often forwards but also upwards. Systemic administration of apomorphine (0.7-2.0 mg/kg s.c.) given 20 min earlier increased the number of rats that displayed the so-called 'running and jumping' behaviour after picrotoxin (0.1-0.2 microgram). The dose-effect curve, however, varied according to the brain structure selected. Systemic administration of morphine (1.0-10.0 mg/kg i.p.) was found to reduce the occurrence of running and jumping behaviour when it was elicited via the locus coeruleus, but not the superior colliculus and central grey. It is suggested that the running and jumping behaviour which is elicited via the locus coeruleus might be a suitable model of a partial morphine abstinence syndrome, i.e. withdrawal jumping, in experimental animals not exposed to any opiate. The superior colliculus and central grey appear to be involved in mediating an opiate-unrelated phenomenon of 'withdrawal' jumping in rats not exposed to any opiate.

Animals↗
PubMed1983

Involvement of the septum in central dopamine-acetylcholine interactions in morphine-treated cats.

The involvement of the septum in central dopamine-acetylcholine (DA-ACh) interactions was investigated by analysis of the behavioural effects of intracerebrally injected drugs in cats pretreated with morphine (5 mg/kg, IP). The intracerebrally evoked effects on the morphine-induced behaviour were analyzed both quantitatively (changes in the incidence of locomotor patterns) and qualitatively (changes in the stereotyped nature of the behaviour patterns). Activation of a particular subclass of dopamine receptors (DAi receptors) within the septum by means of the DAi agonist (3,4-dihydroxyphenylamino)-2-imidazoline (DPI) suppressed the effect of intraseptal injections of the cholinergic agonist carbachol. Simultaneous activation of the DAi receptors within the septum and those within the caudate nucleus produced an effect characteristics of activation of septal DAi receptors; the effect characteristic of activation of caudate DAi receptors was suppressed. Analogous results were obtained when the DAi receptors within the septum and those within the caudate nucleus were simultaneously inhibited by the DAI antagonist ergometrine. Finally, it was found that the effect of intraseptal injections of the cholinergic agonist carbachol was suppressed by inhibition of the DAi receptors within the caudate nucleus. In the latter case, the effect characteristic of inhibition of caudate DAi receptors was also suppressed. The present results indicate the existence of interactions between (1) septal ACh activity and septal DAi activity, (2) septal DAi activity and caudate DAi activity, and (3) septal ACh activity . A mechanism of action for the observed interactions is discussed.

Acetylcholine↗
PubMed1983

(3,4-Dihydroxyphenylimino)-2-imidazoline (DPI) and its action at noradrenergic and dopaminergic receptors in the nucleus accumbens of rats: mesolimbic catecholamine receptors and hyperactivity.

Bilateral administration of ergometrine into the nucleus accumbens of rats pretreated 1-3 min earlier with intra-accumbens injections of noradrenaline, phenylephrine, clonidine and phentolamine has been found to produce a normal ergometrine-induced hyperactivity. In contrast, low doses of dopamine and (3,4-dihydroxyphenylimino)-2-imidazoline (DPI) and only high doses of clonidine and phentolamine have been found to attenuate the ergometrine response. These data together with the finding that phentolamine is unable to alter DPI's ability to suppress the ergometrine response provide direct evidence that the latter DPI effect is certainly not due to its ability to act as an agonist at alpha-NE receptors within the nucleus accumbens of rats.

Animals↗
PubMed1982

Intraseptally injected opiate agents: effects on morphine-induced behaviour of cats.

Behavioural effects of intraseptally administered opiate agents were analyzed in cats pretreated with an intraperitoneal injection of morphine. In this way, it became possible to investigate (1) the involvement of septal opiate receptors in the behavioural response of cats to systemic administration of morphine, and (2) the pharmacological character of septal opiate receptors. The following results were obtained with intraseptal injections 15-16 min after intraperitoneal morphine: (1) naloxone decreased frequencies of head and limb movements, and (2) morphine was ineffective. The following results were obtained with intraseptal injections 40-41 min after intraperitoneal morphine: (1) beta-endorphin and, to a lesser extent, fentanyl increased frequencies of locomotor patterns, (2) morphine and Met-enkephalin were ineffective, (3) naloxone and naltrexone decreased frequencies of locomotor patterns in a dose-dependent way, (4) naloxone and naltrexone antagonized the effects of beta-endorphin and fentanyl, and (5) morphine did not attenuate the effect of naloxone. The intraseptal injections affected only the frequencies of the systemically evoked behaviour patterns; the nature of the behaviour patterns remained unchanged. It is concluded that (1) systemically administered morphine does not affect behaviour via a direct action on septal opiate receptors, and (2) the receptors mediating the septally evoked effects are most probably epsilon-type opiate receptors. The hypothesis is put forward that systemic administration of morphine results in an increased release of beta-endorphin from hypothalamo-septal neurons and, as a consequence, changes the beta-endorphin activity at the epsilon-type opiate receptors in the septum.

Animals↗