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Biomedical subjects

T W Robbins

Publications and source records attributed to T W Robbins.

At least 289 records · Page 16Linked to original sources
PubMed1989

Comparative effects of quisqualic and ibotenic acid-induced lesions of the substantia innominata and globus pallidus on the acquisition of a conditional visual discrimination: differential effects on cholinergic mechanisms.

Two experiments tested the hypothesis that the deficits in conditional discrimination learning produced by ibotenic acid-induced lesions of the ventral pallidum and substantia innominata are produced by loss of the magnocellular cholinergic cells in the nucleus basalis and adjacent regions. Experiment 1 replicated the previously reported deficit in conditional learning produced by ibotenate-induced lesions of the ventral pallidum/substantia innominata, but failed to demonstrate any restoration of learning by a subchronic regimen of the acetylcholinesterase inhibitor physostigmine sufficient to produce significant (30%), but equivalent, degrees of inhibition in the frontal cortex of ventral pallidum/substantia innominata-lesioned or sham-operated rats. Experiment 2 examined the effects of quisqualic acid-induced lesions of the ventral pallidum/substantia innominata. According to most of the measures of learning employed, the quisqualic acid-induced lesion of the ventral pallidum/substantia innominata failed to impair conditional learning, even though the quisqualate-induced lesion produced greater degrees of cholinergic neuron destruction than the ibotenate-induced lesion, as measured in terms of reductions in cortical choline acetyltransferase activity (44% vs 27%). Although consideration of individual data suggested that very high (60%) levels of choline acetyltransferase reduction in Experiment 2 might have detrimental effects of conditional learning, the overall failure of the quisqualate-induced lesions of the ventral pallidum/substantia innominata to impair learning is to be contrasted with the significant behavioural effects of ibotenate-induced lesions. Histological and immunocytochemical analysis showed that the quisqualate-induced lesion, unlike that produced by ibotenate, tended to produce less damage to the overlying dorsal globus pallidus and to parvocellular neurons of the ventral pallidum/substantia innominata, thus implicating these nonspecific effects of ibotenate-induced lesions in their behavioural effects. The present results question previous interpretations of the behavioural effects of ibotenate-induced lesions of the ventral pallidum/substantia innominata in terms of damage inflicted on the cortically-projecting cholinergic cells of the nucleus basalis, and suggest that quisqualic acid, although also nonspecific in its excitotoxic effects, is nevertheless more selective for producing damage to cholinergic neurons in the ventral pallidum/substantia innominata than ibotenic acid.

Animals↗
PubMed1989

Interactions between the amygdala and ventral striatum in stimulus-reward associations: studies using a second-order schedule of sexual reinforcement.

Bilateral, N-methyl-D-aspartate-induced lesions of the basolateral region of the amygdaloid complex in male rats resulted in a marked decrease in instrumental responses maintained by a visual conditioned reinforcer in a paradigm in which sexual reinforcement was presented under a second-order schedule. There were no effects of lesions of the amygdala on the unconditioned sexual behaviour of the males, i.e. on behaviour elicited by primary reinforcers. Infusion of D-amphetamine bilaterally into the nucleus accumbens region of the ventral striatum resulted in a dose-dependent amelioration of the decrease in instrumental behaviour maintained by a conditioned reinforcer which followed lesions of the amygdala. This effect of D-amphetamine critically depended upon the presentation of the conditioned reinforcer (a previously neutral light which had gained reinforcing properties through its prior association with sexual interaction). The results indicate that the basolateral region of the amygdala may interact with dopamine-dependent processes in the ventral striatum in mediating the control by conditioned reinforcers over instrumental behaviour.

Amphetamines↗
PubMed1989

Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum.

The involvement of the amygdala in the potentiation of responding for conditioned reinforcers following intra-accumbens amphetamine injections has been studied. Thirsty rats were trained to associate a light-noise compound stimulus with water and then implanted with guide cannulae in the nucleus accumbens. Half of these rats received excitotoxic lesions of the basolateral region of the amygdala by accumbens. Half of these rats received excitotoxic lesions of the basolateral region of the amygdala by infusing N-methyl-D-aspartate, whereas the other half received infusions of the vehicle. In the test phase, water was no longer presented but responding on one of two novel levers produced the light-noise compound (the conditioned reinforcer) whereas responding on the other lever had no effect. The two groups received four counterbalanced intra-accumbens infusions of amphetamine (3, 10 and 30 micrograms /microliter) or vehicle over four test days. Intra-accumbens amphetamine infusions dose-dependently increased responding on the lever providing a conditioned reinforcer but had no significant effect on responding on the lever which did not produce the conditioned reinforcer. Compared with controls, the lesioned group exhibited a significant, selective reduction in responding on the lever providing a conditioned reinforcer, with no change on the lever on which responding had no consequence, irrespective of drug or control treatment. Control experiments showed that the amygdala lesioned animals were not hypodipsic and exhibited similar levels of hyperactivity following intra-accumbens infusions of D-amphetamine. Furthermore, the capacity to discriminate the conditioned stimulus as well as to acquire a new motor task was not altered by the lesion. These results indicate a role for the amygdala in mediating the effects of stimulus-reward associations on behaviour, via an action on dopamine-dependent mechanisms of the ventral striatum.

Amphetamines↗
PubMed1989

Attenuation of amphetamine-stereotypy by mesostriatal dopamine depletion enhances plasma corticosterone: implications for stereotypy as a coping response.

The relationship between amphetamine-induced stereotyped behavior and a neuroendocrine index of arousal, plasma corticosterone (CCS), was investigated. 6-Hydroxydopamine lesions of the caudate-putamen, which produced dopamine depletions of 60%, blocked stereotypy and prolonged the elevation in corticosterone associated with d-amphetamine treatment (5 mg/kg). Similar dopamine depleting lesions of the nucleus accumbens, which attenuated the locomotor, but not the stereotypic, response to AMPH did not have this effect on CCS. This pattern of results supports the hypothesis that stereotypy has a coping function which may serve to alter arousal and further suggests important differences between the nigrostriatal and mesolimbic dopamine projections in modulating the responsiveness of the neuroendocrine system. These results have implications for understanding the function of behavioral stereotypies common to a number of psychopathological conditions, including schizophrenia and childhood autism.

Adaptation, Psychological↗
PubMed1989

Elementary processes of response selection mediated by distinct regions of the striatum.

The relative contributions of the medial and lateral caudate putamen to performance of a visual reaction time task were compared by examining the effects of unilateral ibotenate-induced lesions to these regions in the rat. Different groups of rats were trained to respond either towards (Discrimination 1) or away from (Discrimination 2) unpredictable, brief visual stimuli presented to either side of the head. Lateral striatal lesions produced a strong spatial bias towards the side of the lesion but left the latency for the initiation of responses to the visual cues unchanged. By contrast, the medial striatal lesions resulted in a smaller degree of spatial response bias but a significant slowing of initiation latency to the side contralateral to the lesion. These effects were irrespective of the side of the stimulus presentation and thus represent response-related impairments. The lesions were further dissociated in their effects on responding inappropriately to task requirements. These results demonstrate a double dissociation of behavioral effects of lateral and medial striatal damage that can be used to infer the operation of distinct elementary processes of response output within a single task. They are important not only in demonstrating functional effects of hypothetical segregated parallel corticostriatal loops but also in showing that these loops must interact to produce integrated performance.

Acetylcholinesterase↗
PubMed1989

Deficits in response space following unilateral striatal dopamine depletion in the rat.

Hungry rats were trained to report the occurrence and location of brief, unpredictable visual stimuli presented to the left of their heads in 1 of 2 response locations. After training, they received unilateral infusions of 6-hydroxydopamine, depleting dopamine throughout the head of the caudate putamen, either on the left or the right side, that is, either ipsilateral or contralateral to the side on which they were required to respond. Following an ipsilateral lesion there were no impairments in localization of the visual discriminanda and there was no lengthening of reaction time. The contralaterally lesioned rats, however, showed considerably lengthened reaction times to both stimuli and a profound bias to the nearer of the 2 response locations. Evidence from probe trials in which the visual stimuli were presented separately or simultaneously showed that the impairment was not due to a failure to localize the stimuli in contralateral space but, rather, resulted from a deficit in directing responses in contralateral space. It is suggested that this may be due to a distortion in the representation of response space.

Animals↗
PubMed1988

Cortical lateralization of function in rats in a visual reaction time task.

Rats were trained to orient to a visual cue presented in either visual field. An asymmetry in reaction time showed that they used one eye to control responses to both visual fields. Cortical removal contralateral to this dominant eye produced a severe and permanent response deficit. Cortical removal ipsilateral to the dominant eye caused a mild and temporary change. Thus, in the rat, there is a functional lateralization that is similar to that seen in humans.

Animals↗
PubMed1988

Distribution and some projections of cholinergic neurons in the brain of the common marmoset, Callithrix jacchus.

The distribution of choline acetyltransferase-immunoreactive (ChAT-IR) neurons was studied in the brain of the common marmoset by using immunohistochemistry. ChAT-IR neurons were found in the medial septal nucleus, vertical and horizontal limb nuclei of the diagonal band, the nucleus basalis of Meynert, pedunculopontine nucleus and laterodorsal tegmental nucleus, and also in the striatum, habenula, and brainstem cranial nerve motor nuclei. The organization of ChAT-IR neurons in the basal forebrain, midbrain, and pons is consistent with the Ch1-Ch6 nomenclature introduced by Mesulam et al. ('83). The combination of the retrograde transport of HRP-WGA with ChAT immunohistochemistry revealed the distribution of neurons in the Ch4 cell group projecting to the dorsolateral prefrontal cortex. The activity of ChAT was highest in limbic cortical structures, such as the hippocampus, and lowest in association areas of the neocortex. Lesions at various loci in the basal forebrain resulted in differential patterns of ChAT loss in the cortex, which suggests some degree of topographical organization of Ch4 projections to the cortical mantle.

Animals↗
PubMed1988

Effects of diazepam, FG 7142, and RO 15-1788 on schedule-induced polydipsia and the temporal control of behavior.

Although benzodiazepine agonists and inverse agonists have opposite effects on drinking elicited by water deprivation, there is much less information about the effects of these drugs on nonhomeostatic drinking. In this experiment the effects of diazepam (0.3-5.0 mg/kg), a benzodiazepine receptor agonist, and FG 7142 (1.0-9.0 mg/kg), an inverse agonist, were determined on drinking elicited by a FT-60 schedule of food delivery (SIP). Both diazepam and FG 7142 dose-dependently reduced SIP, measured as either licking or volume consumed. In addition, diazepam reduced panel pressing for food, decreased locomotor activity, and changed the time course of each behavior. In contrast, FG 7142 reduced schedule-induced drinking without significantly altering other behaviors. The antagonist RO 15-1788, when given in combination with these drugs, only partially restored the reductions in licking produced by diazepam, but was much more effective in reversing the effects of FG 7142 at doses of the antagonist that failed by themselves to affect responding. The opposite pattern of effects was seen on the volume of water consumed. These effects are discussed in terms of the behavioral and pharmacological specificity of these drugs.

Animals↗
PubMed1988

Lesions of the dorsal noradrenergic bundle simultaneously enhance and reduce responsivity to novelty in a food preference test.

In conclusion, DNAB lesions have been shown to have two, apparently contradictory effects in a food preference test: to increase neophobia to a novel environment, and to increase the tendency to eat novel food in a novel environment. It has been suggested that these two effects occur because, although NA has a common action on neuronal firing in terminal fields, the dissociable consequences reflect the different functions of areas in receipt of these noradrenergic afferents. In addition, it has been shown that DNAB lesions, VNAB lesions, and a benzodiazepine, chlordiazepoxide, all have somewhat different behavioral effects in the food preference test. Taken together with the lack of correlation between the various behavioral measures used in these experiments, this suggests that neophobia does not reflect a single behavioral process, such as anxiety, or reactivity to novelty.

Adrenergic Fibers↗
PubMed1988

The relationship between schedule-induced polydipsia and pituitary-adrenal activity: pharmacological and behavioral manipulations.

The relationship between schedule-induced polydipsia (SIP) and pituitary-adrenal activity in rats was investigated using two different approaches that involved either capitalizing on pre-existing individual differences in the propensity to show SIP, or by inducing differences in plasma corticosterone by behavioral or pharmacological means. Thus, in Expt. 1, SIP was monitored after corticosterone levels were pharmacologically altered with drugs that act at the benzodiazepine receptor. In Expt. 2, the relationship between individual differences in water consumption during SIP and plasma corticosterone levels was determined. In addition, corticosterone levels were determined after the prevention of drinking during SIP. Results indicated an inverse relationship between plasma corticosterone levels and SIP. It was also found that corticosterone levels were significantly higher following SIP with water available than after SIP without water. The implications of these results for previous hypotheses of SIP are discussed.

Animals↗
PubMed1988

A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease.

Groups of patients with dementia of Alzheimer type (DAT) and idiopathic Parkinson's disease, together with age and IQ-matched normal controls, were compared on several computerized tests of visuospatial memory and learning. Two different groups of parkinsonian patients were studied: (1) a newly diagnosed group, early in the course of the disease, not receiving medication (NMED) PD) and (2) a group later in the course of the disease, receiving medication (MED PD). The DAT and MED PD group were significantly impaired in both spatial and visual pattern recognition memory. The DAT group exhibited a delay-dependent deficit (over 0-16 s) in a delayed matching-to-sample procedure, but were not impaired at simultaneous-matching-to-sample. By contrast, the MED PD group showed delay-independent deficits in the delayed matching-to-sample test and both the MED PD and the NMED PD group were also significantly impaired in simultaneous matching. In a form of delayed response test, the subjects were required first to memorize and then to learn the locations of several abstract visual stimuli which varied progressively in number from 1 to 8. The DAT group were severely impaired in this conditional associative learning task. A significant proportion of patients, but none of the controls, in the NMED and MED PD group also failed the test at the levels of 6 or 8 items. There was a significant correlation between the performance on the first trial, memory score in the delayed response task and indices of clinical disability and disease duration in the patients with Parkinson's disease. The results are discussed in terms of the utility of the comparison between DAT and PD in characterizing the nature of the cognitive deficits in these conditions and their relation to those findings from animal neuropsychology which use comparable paradigms.

Alzheimer Disease↗
PubMed1988

Planning and spatial working memory in Parkinson's disease.

The higher level cognitive function of planning was studied in a group of medicated Parkinson's disease patients and a group of matched control subjects, using a computerised version of Shallice's Tower of London task. Baseline measurement of the ability to execute a given plan of action, to generate low level strategies required for efficient searching, and spatial working memory capacity, all of which contribute to performance on the planning task, established that the Parkinson's disease group was unimpaired on any of these measures. On the Tower of London task, the Parkinson's disease group was also unimpaired in terms of the average number of moves required to solve a problem. However, a specific planning deficit was evident when "thinking" times were analysed, and this was after the confounding influence of motor initiation and execution times had been carefully extracted from total performance times. This finding is discussed in relation to putative functions of the frontal lobes and basal ganglia, and an attention-switching hypothesis is developed to account for it.

Aged↗
PubMed1987

Noradrenaline- and time-dependent changes in neocortical alpha 2- and beta 1-adrenoceptor binding in dorsal noradrenergic bundle-lesioned rats.

A 6-hydroxydopamine-induced lesion of the dorsal noradrenergic bundle (DNB) in rats markedly decreased neocortical noradrenaline concentration (NNC) by 72-100% as measured 1, 3 and 13 months after the lesioning procedure. The concomitant assessment of neocortical alpha 2- and beta 1-adrenoceptor binding (NAAB and NBAB, respectively) usually indicated significant increases of 25-72% for these two variables. There were, however, cases of unchanged NAAB and NBAB which presumably reflected an incomplete DNB lesion and a consequent time-related, partial recovery of NNC. The results emphasize the potential for long-term sequelae of the DNB lesion, and the existence of a critical NNC threshold (approximately 10-30% of control NNC values) which modulates postsynaptic alpha 2- and beta 1-adrenoceptor density.

Animals↗
PubMed1987

Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: new evidence for central dopaminergic-noradrenergic interactions.

A series of experiments examined the effects of lesions of the dorsal noradrenergic bundle (DNAB), induced by 6-hydroxydopamine (6-OHDA), on the behavioural response to systemic and intra-accumbens amphetamine, using a rat analogue of Leonard's 5-choice serial reaction time task for humans. Although the 6-OHDA DNAB lesion produced a profound depletion of cortical noradrenaline (NA) (to around 5% of control levels) it did not impair any aspect of performance on this task. Both systemic and intra-accumbens amphetamine increased behavioural measures of impulsivity of responding, but neither impaired discriminative accuracy in the sham-operated control rats. However, the DNAB lesioned rats did show a discriminative impairment following both low doses of systemic amphetamine, and intra-accumbens amphetamine. The latter effect was antagonised by systemic administration of the specific dopaminergic (DA) antagonist alpha-flupenthixol. The DNAB lesion did not alter the effect of amphetamine on any other behavioural measure, including speed and impulsivity of responding. These results suggest that although DA and NA participate in qualitatively different behavioural processes, the effects of DNAB lesions on attentional processes depend on the level of DA activity within the nucleus accumbens.

Amphetamine↗
PubMed1987

Comparative functions of the central noradrenergic, dopaminergic and cholinergic systems.

The effects of lesions of the major catecholamine projections and terminal fields induced by 6-hydroxydopamine (6-OHDA), and of lesions of the cholinergic cells in the ventral pallidum/substantia innominata induced by ibotenic acid were compared within a single behavioural paradigm, the acquisition and performance of an appetitive conditional discrimination. Lesions of the coeruleo-cortical noradrenergic pathway induced by 6-OHDA produced over 90% depletion of noradrenaline in the neocortex and hippocampus and led to impairments in the acquisition, but not performance of the discrimination. Depletion of noradrenaline (NA) in the hypothalamus, produced by lesions of the rostral medullary noradrenergic cells, had no effect. Lesions of the caudate-putamen induced by 6-OHDA produced about an 80% depletion of dopamine and led to profound deficits in both the acquisition and performance of the discrimination, also retarding the latency to collect earned food pellets. Lesions of the nucleus accumbens, producing 80% depletion of dopamine from this structure had no significant effect on the acquisition or performance of the task. Lesions of the cholinergic cells in the ventral pallidum/substantia innominata induced by ibotenic acid, depending upon their size, had significant effects on the acquisition and performance of the discrimination, without affecting the latency to collect the pellets. Various problems of interpretation are discussed and the utility of a comparison of the different patterns of the effects of these lesions of catecholaminergic and cholinergic projections is made clear.

Acetylcholine↗