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S D Iversen

Publications and source records attributed to S D Iversen.

At least 163 records · Page 9Linked to original sources
PubMed1981

Learning impairments following selective kainic acid-induced lesions within the neostriatum of rats.

In two separate experiments, rats with kainic acid-induced lesions of the anteromedial (AMC) or ventrolateral (VLC) caudate nucleus were compared with controls on various discrete-trial maze and runway tasks: (a) the AMC lesion disrupted the direction but the degree of spontaneous bias in a T-maze, whereas the VLC disrupted the degree of bias but not its direction; (b) the AMC rats were impaired in the acquisition and reversal of a spatial position habit; (c) the VLC rats were impaired in runway extinction; (d) both lesion groups showed enhanced levels of activity when tested under the same conditions of food deprivation, but did not differ from controls when under free-feeding conditions. The histological analysis suggested that kainic acid does permit the selective lesioning of cell bodies in the neostriatum, whilst sparing fibres of passage. It was concluded that the results demonstrate functional heterogeneity within the neostriatum of rats, in direct agreement with the predictions of the 'prefrontal systems' hypothesis of Rosvold [48, 49].

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PubMed1981

Motor control.

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Animals↗
PubMed1980

Reinnervation of the denervated striatum by substantia nigra transplants: functional consequences as revealed by pharmacological and sensorimotor testing.

Embryonic substantia nigra (SN) was transplanted to the neostriatum in adult rats subjected to a unilateral or serial bilateral destruction of the nigrostriatal dopamine (DA) pathway. The survival of the graft and the growth of DA-containing fibers from the graft into the host brain was studied by fluorescence histochemistry and micro-fluorometry. The motor asymmetry, and the contralateral 'sensory neglect' induced by a unilateral destruction of the nigrostriatal DA pathway, were monitored in the transplanted rats and in non-transplanted controls through repeated measurements of the amphetamine-and apomorphine-induced rotational behaviour, and through analysis of the rats performance in a number of sensorimotor tests. Finally, the development of aphagia and adipsia after a serial bilateral destruction of both nigrostriatal DA pathways were followed in rats bearing bilateral SN transplants and in lesioned non-transplanted controls. The results show that large parts of the dorsal neostriatum can be reinnervated by DA-containing axons from the intracortical transplant and that this new DA input can fully compensate for the amphetamine-induced motor assymmetry that resulted from the initial destruction of the innate nigrostriatal DA pathway. The fluorescence microscopical observations provide strong evidence that the compensation of the amphetamine-induced rotational response was specifically related to the re-establishment of a new DA input to the denervated neostriatum, and that the degree of rotational compensation was well correlated to the magnitude of ingrowth into the neostriatum. Subsequent surgical removal of the SN transplant reinstated the initial rotational behaviour. In sharp contrast to the marked compensation in motor asymmetry, the transplanted rats showed no tendency to recover in their sensorimotor performance. Thus, while the sensorimotor deficit had recovered in the control group a marked contralateral 'sensory neglect' remained in the transplanted animals. Furthermore, removal of the transplant produced a significant improvement in their sensorimotor performance within 3 days. In the bilaterally transplanted animals the presence of the transplants did not prevent the development of severe adipsia, aphagia and akinesia following the destruction of the remaining contralateral nigrostriatal pathway. In fact, the recovery from the consummatory deficits tended to be better in the lesioned control rats than in the transplanted ones. It is concluded that SN transplants reinnervation the dorsal part of the neostriatum are able to replace the innate SN in normalizing some aspects of the rats motor behaviour, while their sensorimotor deficits and deficits in consummatory behaviour were unaffected. It is suggested that this dissociation of transplant-induced recovery is due to the failure of the SN transplants to reinnervate those parts of the neostriatum which are most directly implicated in sensorimotor and consummatory behaviour.

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PubMed1980

Opiate receptors influence vasopressin release from nerve terminals in rat neurohypophysis.

A previous report described the existence of substantial amounts of enkephalin immunoreactivity and the occurrence of nerve terminals containing an enkephalin-like material in the pars nervosa of rat pituitary. It was suggested that an enkephalin innervation of the pars nervosa originating from the magnocellular hypothalamic nuclei might regulate the secretion of neurohypophyseal hormones. The results of the present studies support this hypothesis, as we find that a stable enkephalin analogue (D-Ala 2,D-Leu5-enkephalin) inhibits the calcium-dependent release of vasopressin evoked by electrical stimulation of the rat pituitary stalk in vitro. A similar inhibition of the stimulus-evoked vasopressin release is caused by morphine and beta-endorphin, and the inhibitory effects of the enkephalin analogue can be reversed by naloxone. These findings suggest the possible existence of inhibitory opiate receptors on the terminals of vasopressin fibres in the pars nervosa.

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PubMed1980

An observational method for quantifying the behavioural effects of dopamine agonists: contrasting effects of d-amphetamine and apomorphine.

A novael means of measuring and analysing behavioural effects of dopamine agonists is described and illustrated by a comparison of the effects of d-amphetamine and apomorphine in the rat. d-Amphetamine (0--15 mg/kg IP) produced significant dose- and time-dependent changes in responses such as locomotion, rearing and sniffing, but not in licking or gnawing. In contrast, apomorphine (0--5 mg/kg SC) produced significant increases in licking and gnawing, as well as in locomotion and sniffing, but no changes in rearing. The results are discussed in comparison with those obtained by other methods, such as photocell beam interruptions or sterotypy rating scales, and may be of importance in elucidating the functions of the forebrain dopamine projections.

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PubMed1980

Amylobarbitone and forgetting.

In an earlier report (Hulme et al. 1979), we argued that sodium amylobarbitone (SAB) affects the acquisition of information. That conclusion was based on the finding that SAB produces rates of forgetting that are similar to control, thereby ruling out storage (and possibly retrieval) deficiencies which would predict dissimilar rates. However, it is possible that the rate of forgetting is itself influenced by the amount of information that actually entered store in the first place, and SAB reduces this by affecting acquisition. The possibility that both acquisition and storage could therefore have been affected was explored by equating control and drug zero delay performance, which was achieved by lowering the performance of control subjects. Nonetheless, subsequent rates of forgetting remained similar, thereby strengthening the acquistion hypothesis.

Amobarbital↗
PubMed1980

Ethanol affects the acquisition of information.

Two experiments were carried out on pigeons to assess the effects of acute ethanol (ETOH) administration on a delayed pair comparison procedure. ETOH disrupted performance at the two higher doses (1.0 and 2.0 g/kg, given orally). When the initial (zero delay) performance levels of treated and untreated birds were equated by (indirectly) varying the to-be-remembered stimulus' exposure duration, it was found that the impairment could, to a point, be overcome. This finding is interpreted in terms of hypothesis which suggests that ETOH affects the acquisition but not the subsequent storage of information.

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PubMed1980

Regulatory impairments following selective kainic acid lesions of the neostriatum.

Kainic acid lesions were made to the anteromedial (AMC) or ventrolateral (VLC) caudate nucleus and the projection areas of medial and sulcal prefrontal cortex (PFC), respectively. By the second day following lesion, all control and AMC rats had recovered normal food and water intake. By contrast, VLC lesions resulted in severe aphagia and adipsia lasting 3-15 days, accompanied by a rapid loss in weight. Animals were kept alive by palatable food supplement and force-feeding as required. Once all animals had recovered normal food and water intake (3-5 weeks) drinking to various physiological challenges--5% hypertonic saline s.c., food deprivation, quinine adulteration of water and 40% polyethylene glycol--were found to be normal in both lesion groups. By 3 months after lesion the groups did not differ in weight. Acute aphagia and adipsia had been reported following ablation of the sulcal but not the medial PFC in rats. The present experiment obtains parallel results in the PFC projection areas within the neostriatum.

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PubMed1980

Recognition memory, chlordiazepoxide and rhesus monkeys: some problems and results.

Monkeys were taught a variation of the Konorski [26] pair comparison task, with and without delay, by first training them on a 'simultaneous' procedure involving the judicious use of both correction and non-correction training. In this task, they had to respond to a left hand panel if two simultaneously present colour (green or red) stimuli were the same (e.g. green, green) and to a right hand panel if they were different (e.g. red, green). Once they had learned this task, delays ranging from 0 to 16 sec were interposed between the two stimuli, and reliable forgetting curves were obtained. The effects of chlordiazepoxide (CDP) on such behaviour were assessed in the next experiment. Few impairments were observed even after high (80 mg/kg, i.p.) doses of the drug, and this is in contrast to our previously reported findings with pigeons [31]. However, it was argued that the stimulus presentation times could have been too long, thereby enabling the animal to overcome any deficiency in mnemonic processing. This problem was tackled in the third experiment, by presenting the to-be-remembered stimulus for brief periods; in addition, signal detection performance was also assessed. In spite of such refinements, CDP (30 mg/kg) failed to disrupt percent correct performance on the tasks although response latencies showed an increase, leading in some cases to a failure to respond within the allocated time.

Animals↗
PubMed1980

Interactions between D-ala-met-enkephalin, A10 dopaminergic neurones, and spontaneous behaviour in the rat.

We have investigated the interaction between opioid peptides and dopaminergic A10 (DA-A10) neurones in the ventral tegmental area (VTA). The behavioural consequences of VTA infusion of d-Ala-Met-enkephalinamide (DALA) were analyzed. DALA elicited a dose-dependent increase in locomotor activity measured in photocell cages and the circular corridor. Observations in the open field and in a hole box revealed that DALA-induced behavioural stimulation was characterized by enhancement of locomotion, rearing, and number of hole visits, while grooming time and duration of hole visits were decreased. DALA-induced stimulation was reserved by naloxone, and was completely blocked by 6-OHDA destruction of DA-A10 terminals. d-Amphetamine-induced behavioural activation was potentiated by simultaneous VTA infusion of DALA which indicates that the behavioural response to DALA is dependent on DA-A10 neuronal activity. It is postulated that stimulation of opiate receptors exerts a presynaptic inhibition of an inhibitory input to DA-A10 neurones (eg. GABA or dendritic DA), thus releasing dopaminergic activity. In contrast to the acute effect, the d-amphetamine response was strongly attenuated 4 h, 1 and 6 days after VTA infusion of DALA, and returned to normal only at 14 days. This long-lasting modification may reflect decreased activity of opioid neurones, releasing the inhibition of DA-A10 neurones. Our findings suggest that endogenous opioid peptides may exert a modulatory influence on the dopaminergic mesocorticolimbic system.

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PubMed1980

Brain chemistry and behaviour.

The functional organization of chemically transmitting synapses in the brain are described with special emphasis on recent studies demonstrating the localization of different transmitters to specific anatomical circuitries. The use of pharmacological tools for manipulating levels of chemical transmitters is referred to briefly, but particular attention is given to the problems of studying the function of these pathways with lesion techniques. Noradrenaline (NA) and dopamine (DA) are selected for detailed consideration and experimental evidence reviewed, suggesting that these two catecholamines in the forebrain serve different functions: NA with processes of attention essential for learning, and DA with the execution of appropriate responses. Hypotheses suggesting dysfunction of forebrain DA and NA systems in schizophrenia are discussed.

Animals↗
PubMed1980

Animal models of anxiety and benzodiazepine actions.

If rats trained to press a lever for food, then receive a shock to the feet following every response, their behavioural output is severely depressed. This procedure is termed immediately punishment and it was used by Geller and Seifter in the task devised to demonstrate the anxiolytic effect of benzodiazepines. These drugs and a number of others with anxiolytic activity (e. g. barbiturates, ethanol) reverse the suppression induced by the presentation of a highly aversive stimulus, like electric shock. The Geller-Seifter procedure has figured prominently in behavioural studies of benzodiazepines and in the efforts to determine the neuropharmacological basis of their anxiolytic action. Experiments involving the manipulation of brain noradrenaline (NA) and 5-hydroxytryptamine (5-HT) levels with drugs or lesions are discussed. The Geller-Seifter procedure is, however, a time consuming and difficult behavioural baseline to work with. It is important, therefore, to devise equally specific but simpler animal models of anxiety. Electric shock, as the anxiety-inducing event has dominated the tasks devised by behavioural psychologists. It is essential to search for more biologically relevant events with which to control the level of anxiety in experimental animals. Tests involving the manipulation of novelty and uncertainty will be presented and their responsiveness to anxiolytic drugs and neuropharmacological manipulation discussed. Recent advances in defining the biochemical and pharmacological properties of benzodiazepine receptors and particularly of their differential distribution in brain, makes it likely that simple reliable animal tests of anxiety would serve neuropharmacology well and be of great value in understanding the functional importance of the benzodiazepine receptors of brain.

Animals↗
PubMed1979

Substance P infusion into substantia nigra of the rat: behavioural analysis and involvement of striatal dopamine.

The purpose of the present study was to characterize the nature of the behavioural response to substance P (SP) infusion into the substantia nigra and to evaluate this response in 6-hydroxydopamine (6-OHDA) caudate lesioned rats. The effects of SP infusions (3 microgram in 1 microliter bilaterally) were assessed in an open field. Two groups of rats were used: one with 6-OHDA lesions in the caudate nucleus, and one with sham lesions. In sham rats, the first infusion produced a strong increase in sterotyped rearing and sniffing, with no concurrent enhancement of locomotion. With three subsequent infusions (made at interval of two days) the rearing response disappeared and a tendency to groom emerged. All SP-induced behavioural stimulation was blocked in the caudate-lesioned rats; an effect of the lesion itself was reduced rearing. These results suggest that the response to SP infusion is mediated through the nigro-striatal dopamine system. The behavioural profiles which emerge after SP infusion into the substantia nigra and ventral tegmental area are compared. In general, the behavioural studies of SP effects support the concept that the A9 and A10 dopamine systems can be behaviourally differentiated.

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PubMed1979

Effects of sodium amylobarbitone on memory processes in the pigeon.

An experiment was carried out in the pigeon to assess the effects of sodium amylobarbitone (SAB) on memory, using a delayed pair comparison task. Performance was disrupted at all delays by doses of 10 and 20 mg/kg SAB and it was concluded that this effect was not due to perceptual impairment or stereotyped responding, which the drug might have caused, since performance on a visual discrimination task was unaffected by the same doses of SAB. Two further experiments assessed proactive and retroactive effects by varying the inter-trial interval and by introducing an irrelevant orange stimulus at various stages of the delay interval. Although these manipulations disrupted performance, there was no evidence to suggest that the drug potentiated their effects in a specific manner. The results are discussed in terms of an encoding hypothesis, and some reference is made to the possible neuropharmacological basis of action of this drug.

Amobarbital↗
PubMed1979

Restricted posterior parietal lesions in the rhesus monkey and performance on visuospatial tasks.

Monkeys with lesions restricted to the inferior parietal lobule or the banks and depths of the superior temporal sulcus were tested on a route-following task. These areas are considered on neuroanatomical grounds to be homologous to parts of the human posterior parietal cortex, where lesions produce profound spatial disorientation. The operated monkeys were impaired on the route task, thus confirming at the behavioural level the anatomical predictions of comparability between parietal cortex in monkey and that in man. The monkeys were not impaired, however, on a visual pattern discrimination or on a visual-spatial task with cue and response separation, a task that was considered on the basis of previous investigations with extensive posterior lesions in the monkey to be sensitive to parietal lesions.

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PubMed1979

Theories of the dorsal bundle extinction effect.

Selective destruction of the noradrenaline systems in the rat brain using the neurotoxin 6-hydroxydopamine has been found to cause resistance to extinction in a number of behavioural situations. Several theories concerning the behavioural mechanism altered by the lesion, and hence about the role of noradrenaline in normal brain functioning, are proposed and evaluated. Theories suggesting a role for noradrenaline in activity, perseveration, internal inhibition, frustrative non-reward, motivation, or secondary reinforcement, fail to explain all the available evidence and direct tests of each theory fails to support its predictions. A model which suggests that noreadrenaline is involved in attentional behaviour, specifically in filtering out or learning to ignore irrelevant environmental stimuli, is successful in explaining all available data and direct tests of the lesioned rats' attentional capacity serve to confirm many of the predictions of an attentional theory of the dorsal bundle extinction effect.

Animals↗
PubMed1979

Behavioural activation induced in the rat by substance P infusion into ventral tegmental area: implication of dopaminergic A10 neurones.

The functional role of the putative transmitter substance P (SP) was studied using a behavioural approach. SP infusion into the ventral tegmental area in awake rats elicited an increase in locomotor activity which could be blocked by either infusion of a neuroleptic into the nucleus accumbens septi (NAS) or by 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic A10 neurones. Our results suggest that SP induces its behavioural effects through activation of dopaminergic A10 neurones, and imply that endogenous SP may have an important modulatory role.

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