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Biomedical subjects

A R Cools

Publications and source records attributed to A R Cools.

At least 235 records · Page 13Linked to original sources

Subcutaneous injections of apomorphine, stimulus generalization and conditioning: serious pitfalls for the examiner using apomorphine as a tool.

This report shows that stimulus generalization occurs in rats conditioned by a single injection of apomorphine. The data suggest that apomorphine initially acts as an unconditioned stimulus (UCS) of an unconditioned response (UCR) that, in turn, produces stimuli which become conditioned stimuli (CS) of a conditioned response (CR) having a nature identical to that of the UCR. The study also shows that behaviour elicited by a subcutaneous injection of apomorphine depends on the part of the body selected for administration. The mentioned properties should be taken into account when apomorphine is used as a tool in studies on brain and behaviour.

Animals↗

Excitation-mediating and inhibition-mediating dopamine-receptors: a new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data.

A great number of earlier reported experimental data dealing with the role of dopamine in dopamine-loaded structures within the mammalian brain have raised questions concerning the concept of dopamine as an inhibitory agent acting on one type of receptor. A critical review of the anatomical, histochemical, electrophysiological, pharmacological and functional studies reveals that the dopamine-loaded structures are marked by an internal differentiation at various levels. It is attempted to demonstrate that this is due to a heterogeneous distribution of two distinct types of dopamine-receptors, each characterized by their own properties: DAe and DAi-receptors. Furthermore, the experimental and clinical implications are discussed in view of the hypothesis that balance between both types of receptors is essential for normal psychomotor functioning.

Amphetamines↗

Dopamine receptors: selective agonists and antagonists of functionally distinct types within the feline brain.

Unilateral injections of agents that are useful tools for differentiating electrophysiologically distinct dopamine receptors within the snail Helix aspersa are given into behaviourally distinct dopamine sensitive areas within the caudate nucleus of cats. Dopamine-elicited contralateral head-turning is selectively mimicked by apomorphine and selectively inhibited by haloperidol, whereas dopamine-elicited homolateral head-turning including oro-facial dyskinesias is selectively mimicked by (3, 4-dihydroxy-phenylamino)-2-imidazoline (DPI) and selectively inhibited by ergometrine, piribedil and noradrenaline. These results indicate that the caudate nucleus of cats contains two functionally and pharmalogically distinct dopamine receptors and that Helix aspersa dopamine sensitive neurons can be used as model for the design of drugs selectively interfering with each type of receptor. The implications of these findings are considered in view of the efficacy of piribedil, L-DOPA and neuroleptics in psychomotor diseases in man.

Acetylcholine↗

Separation of inhibiting and stimulating effects of morphine on self-stimulation behaviour by intracerebral microinjections.

The effects on self-stimulation behaviour of 5 mug morphine HCl applied into the ventricular system and into different areas throughout the brain were studied. Injections into the ventricular system and in areas intermediate between the posterior hypothalamus and the periaqueductal grey matter had biphasic effects: an inhibition followed by an excitation. Injections into the posterior hypothalamus resulted in increased self-stimulation whereas injections into the periaqueductal grey matter and into the locus coeruleus were only inhibiting.

Animals↗

Further investigations on the effects of ergometrine and other ergot derivatives following injection into the nucleus accumbens of the rat.

The influence of different pretreatments upon locomotor stimulation, induced by injection of ergometrine into the nucleus accumbens of rats, was investigated. The noradrenergic antagonists phenoxybenzamine and propranolol and the serotonin antagonist methysergide produced no clear changes. Reserpine, alone or in combination with alpha-MPT, considerably shortened the delay between injection of ergometrine and start of locomotor stimulation. Ro-DOPA, but not Ro-5-HTP, clearly antagonized the locomotor stimulation. The effect of ergometrine was strongly diminished following injection of haloperidol directly into the nucleus accumbens. A strong inhibition was also observedfollowing intracerebral administration of the imidazoline derivative (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI), but not after injection of the structurally related compound clonidine. DPI by itself and also the ergot derivatives ergocornine, bromocryptine, LSD, dihydroergotamine and methysergide in doses 5--10 times as high as that of ergometrine failed to produce locomotor stimulation following injection into the nucleus accumbens. The results are discussed, especially with regard to the role of dopamine.

Animals↗

The effect of microinjections of amphetamine into the neostriatum and the nucleus accumbens on self-stimulation behaviour.

The effect of micro-injections of dexamphetamine chloride into the neostriatum, the nucleus accumbens, the anterior hypothalamus, and the ventricular system on self-stimulation with electrodes in the ventral tegmentum was studied. Unilateral injections of 10 mug into the anterior hypothalamus produced no effect. Injections into the neostriatum tended to depress the self-stimulation rate, whereas injections into the nucleus accumbens increased the rate markedly. Bilateral injections (2 times 2.5 mug and 2 times 5 mug amph.) into the nucleus accumbens were more effective than unilateral injections and were as effective as systemic injections of 1 mg/kg amphetamine (i.p.). Bilateral injections into the neostriatum also increased the self-stimulation rate. Injections of 10 mug into the ventricular system resulted in a smaller increase which was not statistically significant. These results are discussed in relation to the involvement of the dopaminergic system in the maintenance of self-stimulation behaviour.

Animals↗

The acetylcholine-dopamine balance in the basal ganglia of rhesus monkeys and its role in dynamic, dystonic, dyskinetic, and epileptoid motor activities.

Behavioural analyses have been made of effects brought about by both single and combined injections of dopamine, haloperidol, carbachol and atropine into the caput nuclei caudati of rhesus monkeys. High doses of dopamine produced the subsequent development of three types of behavioural changes: an increase in the number of skilled manipulation movements (the dynamic phase); the appearance of a dystonic torticollis (the dystonic phase); and, finally, the appearance of an oro-lingual-facial dyskinesia and a number of dyskinetic activities in the extremities (the dyskinetic phase); low doses of dopamine solely produced the dynamic phase. Haloperidol only inhibited the dopamine-induced dynamic and dystonic phase: it did not suppress the dyskinetic phase. High doses of carbachol produced the subsequent development of four phases: a dynamic, dystonic, dyskinetic and epileptoid phase; the last one was marked by the appearance of secondary generalized epileptic seizures. Low doses of carbachol solely produced the dynamic phase. Atropine inhibited the carbachol-induced dynamic, dystonic and epileptoid phase; it did not suppress the dyskinetic phase. High doses of dopamine strongly modified the carbachol-induced phases: dopamine intensified the dystonic phase on the one hand, but it abolished the generalized epileptic seizures on the other hand. Apart from the fact that the data presented have confirmed that both dopaminergic and cholinergic mechanisms within the basal ganglia of rhesus monkeys are involved in the elicitation and modulation of both normal and abnormal motor activities, they have also revealed that the simple concept of a stristal acetylcholine-dopamine "see-saw" has to be revised. Furthermore, the data have suggested that development of supersensitive dopamine-sensitive sites is not the only mechanism that underlies the elicitation of the oro-lingual-facial dyskinesia. And finally, the present experiments have given clearcut evidence that an intrastriatal acetylcholine-dopamine "see-saw" fulfils and essential role in the process involved in the generalization of epileptic seizures.

Acetylcholine↗

Chemistor: a reusable telestimulation device for direct chemical stimulation of the nonhuman primate brain in freely moving animals.

A reusable telemetric multi-injector unit (chemistor) suitable for injections into the brain of primates has been developed and tested in chronic experiments with rhesus monkeys freely moving and interacting with other monkeys. The chemistor unit, which measures 15.0 by 15.0 by 7.5 mm and weight 5.8 g, consists of a microinjector, equipped with an internal mechanical power source, and an electronic circuit connected with a receiving coil; a total volume of 27.0 mul to be injected in quanta of 0.9 mul at freely chosen time intervals makes this unit suitable for 30 injections. The desirable protection against possible damage is provided by a circular, head-mounted container (dia. 43.0 mm and 10.3 mm high) which leaves place for two complete chemistors. The device is small, light in weight, reliable and resistant to physical damage.

Animals↗