PubMed Health⌕ Search

Biomedical subjects

S D Iversen

Publications and source records attributed to S D Iversen.

At least 127 records · Page 7Linked to original sources
PubMed1984

Behavioural effects of manipulation of basal ganglia neurotransmitters.

Topographically organized dopaminergic projections from the extrapyramidal structures of the ventral mesencephalon (substantia nigra and ventral tegmental area) to the dorsal (body of caudate-putamen) and ventral (anterior-ventral caudate, nucleus accumbens, tuberculum olfactorium) striatum subserve sensorimotor integration in the rat. Selective depletion of DA impairs the animal's ability to integrate sensory input with motor output; in the dorsal striatum the exteroceptive sensory input and in the ventral or limbic striatum the interoceptive input principally related to motivation and affect. Grafts of fetal DA neurons to the damaged dorsal striatum reverse sensorimotor asymmetry and sensory neglect. A large number of other excitatory and inhibitory neurotransmitters, including recently discovered neuropeptides, contribute to the functional balance afforded by the DA neurons. This chemical heterogeneity of the basal ganglia offers the possibility that novel therapeutic approaches with drugs could be used to control the chemical imbalances in basal ganglia that are associated with a number of neurological and psychiatric conditions.

Acetylcholine↗
PubMed1984

Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination.

In rats, conditioned place preferences are produced by morphine and conditioned place aversions produced by naloxone. In the present studies, several issues concerning the demonstration and interpretation of place conditioning findings were examined in a two-compartment (black and white) tilt box: (1) the responses of naive rats to testing, (2) place conditioning in rats with strong unconditioned biases to one of the sides, and (3) modifications of the testing situation so that naive rats respond to the black and white sides with a minimum of initial bias. Experiments involving manipulation of the conditions of training and testing, use of pentobarbital, and use of a three-compartment test box helped to control for morphine's ability to produce state dependent learning as an explanation of its conditioned place preference. In addition, we examined previous place conditioning studies that failed to show aversive effects of naloxone. These negative findings were suggested to be due to the use or procedures insensitive to aversive stimuli and to the IP administration of naloxone. Finally, in the course of the experiments, novel data on general parameters of the place conditioning were provided. Dose-response curves for subcutaneous (SC) morphine (0.04-5.0 mg/kg) and naloxone (0.02-5.0 mg/kg) were established. Conditioned preferences were also shown to occur after at three pairings of SC drug, and they were retained for at least 1 month.

Animals↗
PubMed1984

Dissociable effects of 6-OHDA-induced lesions of neostriatum on anorexia, locomotor activity and stereotypy: the role of behavioural competition.

The effect of 6-OHDA-induced lesions of neostriatum on locomotor activity, stereotypy and anorexia induced by amphetamine (0.5 mg/kg, 1.5 mg/kg and 5.0 mg/kg IP) was examined. Lesioned rats demonstrated attenuated stereotypy and anorexia but enhanced locomotor activity to amphetamine. Biochemical analysis of dopamine and noradrenaline in specific forebrain areas demonstrated significant dopamine depletion in neostriatum. Dopamine levels in mesolimbic, frontal cortex and hypothalamic areas, and noradrenaline in frontal cortex and hypothalamic areas, were not significantly reduced. The data were interpreted in terms of a response incompatibility hypothesis. It is proposed that stereotyped responses mediated by nigrostriatal dopamine neurones are incompatible with eating. In addition, it is suggested that a second form of competition, at the neuro-anatomical level, occurs between mesolimbic and nigrostriatal systems for motor output pathways and the ultimate expression of behaviour. The role of noradrenaline in amphetamine anorexia is also discussed.

Amphetamine↗
PubMed1984

5-HT and anxiety.

Explore the source record for details and available documents.

5,7-Dihydroxytryptamine↗
PubMed1984

An interactive 24-channel event-logging system based on the AIM 65 single-board microcomputer.

Measures of the spontaneous behaviour of animals commonly involve the repetitive counting of behavioural events over successive periods of time following some experimental treatment. An automated event-logging system has been designed for such applications. The system is based on an AIM 65 microcomputer with 4 Kbytes of random-access memory and facilities for manual event-logging through the keyboard, or automatic logging via a signal-conditioning buffer, connected to the backplane connector of the computer. The control program is written in 6500 machine code and stored in an onboard, read-only, memory chip. The software generates a simple interactive dialogue for the selection of operating options which include manual or automatic modes, configuration of active channels, duration and number of logging cycles, and the choice of printed or transmitted output. The microcomputer can also be instructed to pause and then to restart, to print out its current status, or to abort. The system has been used over a period of 18 months in numerous experiments in this laboratory, and has proved to be reliable, accurate and entirely suited to its application.

Animals↗
PubMed1984

Impairment in T-maze reinforced alternation performance following nucleus basalis magnocellularis lesions in rats.

Rats were trained on a reinforced alternation paradigm using an elevated T-maze. After pre-surgical training subjects received either ibotenic acid (4 micrograms/0.4 microliter) or vehicle (pH 7.4, 0.4 microliter) bilaterally into the region of the nucleus basalis magnocellularis--an important source of neocortical acetylcholine projections. Acetylcholinesterase staining of sectioned brains revealed a loss of neocortical, but not hippocampal staining in lesioned animals. On the T-maze task, lesioned rats showed significantly impaired choice performance relative to controls. They also demonstrated significant side biases, the degree of which was correlated with choice performance deficit.

Acetylcholine↗
PubMed1984

Dopamine denervation of frontal cortex or nucleus accumbens does not affect ACTH-induced grooming behaviour.

Studies with dopamine (DA) receptor antagonists have implicated brain DA systems in the increased grooming behaviour elicited by intracerebroventricular (i.c.v.) administration of ACTH or exposure to a novel environment. To evaluate the potential contributions of DA terminals innervating frontal cortex and nucleus accumbens, stereotaxically guided injections of 6-hydroxydopamine (6-OHDA) were made into these regions of rat brain following peripheral administration of desmethylimipramine and pargyline. Despite an 88% mean reduction of DA, and 68% mean reduction of noradrenaline in frontal cortex, the amount of grooming behaviour observed either in a novel cage, or after i.c.v. injection of ACTH1-24 was not detectably altered. The lesions also did not affect locomotor activity measured during the scoring of grooming, in an open field, in photocell cages, or in a running wheel, even in the animals most severely depleted of DA. Following nucleus accumbens 6-OHDA infusions, depletions of DA as great as 99% were obtained. Animals with accumbens depletions greater than 90% showed the expected attenuation of amphetamine-stimulated locomotor activity. Nevertheless, they exhibited normal grooming scores in a novel cage, and in response to i.c.v. ACTH1-24. It is concluded that dopaminergic terminals in nucleus accumbens and probably those in frontal cortex are not necessary for the expression of novelty- or ACTH-induced grooming.

Adrenocorticotropic Hormone↗
PubMed1984

Hippocampal deafferentation: transplant-derived reinnervation and functional recovery.

A brief review of the capacity of neural tissue transplants to reinnervate the deafferented hippocampus and repair functional deficits induced by the lesion. The techniques for transplantation of solid pieces of embryonic septum, locus coeruleus or raphe nuclei, or tissue suspensions of embryonic septum, to the adult rat hippocampus are described. Such grafts manifest good long-term survival, provide a good reinnervation of the hippocampus that is histochemically and biochemically appropriate and specific, can establish ultrastructural synaptic contacts with the host, and are electrophysiologically active. Rats with septal grafts manifest recovery of the capacity to learn certain aspects of radial 8-arm maze. T-maze alternation and Morris water-maze tasks. Rats with locus coeruleus grafts manifest an amelioration of lesion-induced hyperactivity. It is concluded that neural tissue transplantation provides a powerful new tool in the study of the functional organization of the hippocampus and its various neurotransmitter-specific afferent systems.

Afferent Pathways↗
PubMed1983

Two routes of continuous amphetamine administration induce different behavioral and neurochemical effects in the rat.

Continuous amphetamine administration has proven to be a useful pharmacological tool. The two systems popularly used for the continuous administration of amphetamine differ in their release characteristics; output of drug from passive diffusion silicone-tubing implants gradually declines over several days, while that osmotically driven, active pumps remain more stable over time. A matched-dose comparison of the behavioral and neurochemical effects of both systems was performed in which silicone pellets and pumps were filled with appropriate concentrations of drug so as to release equal total quantities over the test period of 5 days. Rat behavior and brain catecholamine levels were affected in quantitatively and qualitatively different ways. The interesting constellation of behavioral and neurochemical changes associated with the use of silicone-tubing systems for the continuous administration of amphetamine may not be confounded by its declining output, but rather caused by it.

Amphetamines↗
PubMed1983

Nigral transplants reinnervating the dopamine-depleted neostriatum can sustain intracranial self-stimulation.

Transplants of embryonic substantia nigra reinnervated the striatum and were able to sustain intracranial self-stimulation in rats with brain lesions induced by 6-hydroxydopamine. Dopaminergic drugs and alterations in current intensity produced typical changes in response rates. Animals with electrodes implanted into cortical grafts or into the denervated striatum failed to exhibit self-stimulation. These findings suggest that transplanted dopamine neurons convey specific, temporally organized information axonally to the striatum.

Animals↗
PubMed1983

Effect of injections of 6-OHDA into either nucleus accumbens septi or frontal cortex on spontaneous and drug-induced activity.

The effect of injections of 6-hydroxydopamine (6-OHDA) into either frontal cortex (FCx) or nucleus accumbens (NAS) on spontaneous, amphetamine and apomorphine photocell cage activity was studied. Both lesions groups had significant noradrenaline depletion in frontal cortex but only the FCx group had significant dopamine depletion in frontal cortex. Whereas NAS 6-OHDA rats exhibited enhanced apomorphine- and decreased amphetamine-activity there were no differences in activity of the FCx group. 6-OHDA NAS rats also exhibited spontaneous hypoactivity on the third but not the seventh post-operative day; there were no differences in spontaneous activity on either days in the FCx group. In 1975 Kelly, Seviour and Iversen demonstrated that destruction of forebrain dopaminergic terminals induced with injection sof 6-hydroxydopamine (6-OHDA) into the nucleus accumbens septi (NAS) attenuated the locomotor response to 1.5 mg/kg d-amphetamine without affecting stereotypy seen at 5.0 mg/kg. In addition, these rats exhibited an enhanced locomotor response to the dopamine receptor agonist apomorphine, an effect thought to reflect receptor supersensitivity induced by dopamine denervation (Ungerstedt, 1971). Biochemical assay data revealed that dopamine levels were significantly reduced both in nucleus accumbens septi (NAS) and olfactory tubercle (OT) but not neostriatum; thus it was concluded that amphetamine- and apomorphine-induced locomotor activity is mediated by the mesolimbic dopamine system. Since then it has become clear that the A10 group of dopamine (DA) cells bodies in the ventral tegmental area (VTA), give rise to dopamine fibres which innervate not only NAS and OT, but also frontal cortex (Bjorklund and Lindvall, 1978).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

The effects of central catecholamine depletions on spatial learning in rats.

The role of forebrain catecholamine systems in spatial learning was assessed using a recently described place navigation task. Rats were required to learn the spatial location of a platform hidden 1 cm below the surface in order to escape from a large pool filled with opaque water. Circumscribed destruction of dopamine or noradrenaline neurones was achieved with bilateral stereotaxic injections of 6-hydroxydopamine. Rats with neostriatal dopamine depletions showed regulatory impairments, mild akinesia and increased latencies to escape during training on both the spatial task and on a non-spatial control task. However their normal transfer test performance indicated that their deficit was not due to impaired spatial learning. Similarly, spatial learning and transfer test performance were unimpaired by mesocorticolimbic dopamine depletions or by extensive noradrenaline loss in cortex and hippocampus following dorsal noradrenergic bundle lesions. These findings suggest that considerable spatial learning can occur in the absence of each of the major telencephalic catecholamine systems.

Afferent Pathways↗
PubMed1983

The effects of inferotemporal cortex lesions on Konorski delayed pair comparison in monkeys.

Rhesus monkeys were trained on a pair comparison recognition memory task, running concurrently with a signal detection (attention) problem. The animals were given bilateral posterior or anterior inferotemporal cortex lesions once satisfactory performance had been reached. The former group sustained attentional but only transient mnemonic impairments. Anterior lesions impaired visual learning and memory, but not attention. We confirm that inferotemporal cortex is sub-divided into at least two distinct regions, serving visual attention and other cognitive processes. The role of inferotemporal cortex in recognition memory is discussed, and it is concluded that task-related problems do not permit an unambiguous resolution of this question.

Animals↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. IV. Behavioural recovery in rats with unilateral 6-OHDA lesions following implantation of nigral cell suspensions in different forebrain sites.

Single and multiple implants of nigral cell suspensions were grafted to the forebrains of rats with unilateral 6-hydroxydopamine-induced dopamine denervations. Control lesions alone induced a marked behavioural asymmetry, as assessed by amphetamine- and apomorphine-induced rotation, sensorimotor tests and side bias in an unbaited T-maze, and the animals were hyperactive to a low dose of apomorphine. Single suspension placements into different denervated striatal regions were capable of reversing the behavioural asymmetries dependent upon the specific placement for each test. Multiple suspension grafts were capable of reversing all behavioural asymmetries, and additionally abolished the supersensitive hyperactivity to apomorphine. By contrast, single suspension grafts placed into the substantia nigra or lateral hypothalamus had no detectable effect on any functional measure. The results indicate that nigral suspension grafts can be at least as effective as solid grafts in reversing the functional deficits induced by dopamine denervation, provided that placements are selected within appropriate dopamine terminal regions of the forebrain (e.g. caudate-putamen or nucleus accumbens).

Animals↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. V. Behavioural recovery in rats with bilateral 6-OHDA lesions following implantation of nigral cell suspensions.

Bilateral 6-hydroxydopamine-induced lesions of the ascending forebrain dopamine neurones induce a behavioural syndrome in rats which includes profound aphagia, adipsia, akinesia and bilateral sensorimotor neglect. Such animals will die unless maintained by intragastric feeding. Three experiments are reported in which we have attempted to ameliorate this syndrome with single or multiple placements of nigral cell suspensions into the forebrains of rats with bilateral dopamine depletions. Although the grafts were efficient in reversing the sensorimotor and akinetic impairments, and produced a significant increase in eating, the grafted rats remained hypophagic and adipsic. The results indicate that although many components of the bilateral dopamine denervation syndrome can be reversed by intrastriatal nigral suspension grafts, the severe eating and drinking deficits remain unameliorated.

Animals↗
PubMed1982

Septal transplants restore maze learning in rats with fornix-fimbria lesions.

In a study of the capacity of neural grafts to promote functional recovery in rats with fimbria-fornix lesions, 5 groups of rats were studied behaviourally and with acetylcholinesterase (AChE) histochemistry: (1) sham-operated controls; (2) bilateral fimbria-fornix lesions; (3) bilateral lesions plus bilateral solid embryonic septal grafts to the lesion cavity; (4) bilateral lesions plus bilateral embryonic septal suspension injections into the hippocampus; and (5) bilateral lesions plus bilateral solid embryonic locus coeruleus grafts to the lesion cavity. Seven months were allowed for growth of the grafts and reinnervation of the host hippocampus prior to behavioural testing. The control rats were able to rapidly learn a rewarded alternation task, while the performance of animals with bilateral fimbria-fornix lesions alone remained at a chance level. Both types of septal grafts (rich in cholinergic neurones) but not the locus coeruleus grafts (rich in noradrenergic neurones) reversed the impairment. Behavioural recovery correlated significantly with AChE-positive fibre ingrowth from the grafts into the denervated host hippocampus. However, the septal grafts did not ameliorate the lesion-induced disturbances in spontaneous activity or spontaneous alternation. Thus, the observed behavioural recovery appears specific to the conditioned alternation task and dependent upon cholinergic reinnervation of the hippocampus.

Acetylcholinesterase↗