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T W Robbins

Publications and source records attributed to T W Robbins.

At least 199 records · Page 11Linked to original sources
PubMed1996

Dissociations in hippocampal 5-hydroxytryptamine release in the rat following Pavlovian aversive conditioning to discrete and contextual stimuli.

The experiments examined the release of 5-hydroxytryptamine using in vivo microdialysis methods in the hippocampus of freely moving rats following Pavlovian aversive conditioning to discrete and contextual stimuli. Differential conditioning was achieved by manipulating the interval between the offset of a discrete auditory 'clicker' stimulus and the onset of a mild foot-shock reinforcer (0.5 mA, 0.5 s). Foot-shock occurred either simultaneously with the last second of the discrete auditory stimulus (in short-trace subjects) or 60 s later (long-trace subjects). In this way, subjects were preferentially conditioned to the discrete stimulus and background 'contextual' stimuli respectively. During conditioning subjects also received two identical unpaired visual stimuli. At test, dialysates were collected and behavioural measures taken as all animals experienced (i) the aversive and two other 'neutral' environments, and (ii) the discrete unconditioned and conditioned stimuli presented in both aversive and neutral environments. Exposure to the aversive environment, but not to either of the two neutral environments, was associated with significantly increased hippocampal 5-hydroxytryptamine release in long-trace subjects. There was also a small but non-significant increase in 5-hydroxytryptamine release in short-trace animals. In contrast, hippocampal 5-hydroxytryptamine release was unaffected by presentation of either of the discrete stimuli under all conditions. The last result was obtained despite robust behavioural responses (freezing) to the discrete conditioned stimulus. These data do not agree with the hypothesis that aversive cues generally activate 5-hydroxytryptamine function in the hippocampus. Rather, they suggest a degree of specificity whereby 5-hydroxytryptamine release in the hippocampus was determined primarily by other qualitative properties of the conditioned aversive stimulus, namely whether the aversive cue was discrete or contextual, as well as by the magnitude of conditioning.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Working memory in chess.

Three experiments investigated the role of working memory in various aspects of thinking in chess. Experiment 1 examined the immediate memory for briefly presented chess positions from master games in players from a wide range of abilities, following the imposition of various secondary tasks designed to block separate components of working memory. Suppression of the articulatory loop (by preventing subvocal rehearsal) had no effect on measures of recall, whereas blocking the visuospatial sketchpad (by manipulation of a keypad) and blocking the central executive (by random letter generation) had equivalent disruptive effects, in comparison with a control condition. Experiment 2 investigated the effects of similar secondary tasks on the solution (i.e., move selection) of tactical chess positions, and a similar pattern was found, except that blocking the central executive was much more disruptive than in Experiment 1. Experiment 3 compared performance on two types of primary task, one concerned with solving chess positions as in Experiment 2, and the other a sentence-rearrangement task. The secondary tasks in each case were both designed to block the central executive, but one was verbal (vocal generation of random numbers), while the other was spatial in nature (random generation of keypresses). Performance of the spatial secondary task was affected to a greater extent by the chess primary task than by the verbal primary task, whereas there were no differential effects on these secondary tasks by the verbal primary task. In none of the three experiments were there any differential effects between weak and strong players. These results are interpreted in the context of the working-memory model and previous theories of the nature of cognition in chess.

Adult↗
PubMed1996

Excitotoxic lesions of the basolateral amygdala impair the acquisition of cocaine-seeking behaviour under a second-order schedule of reinforcement.

In these experiments we sought to establish the intravenous (i.v.) self-administration of cocaine under a second-order schedule of reinforcement in order: (i) to obtain reliable, drug-free levels of responding with cocaine as a reinforcer, and (ii) to enable investigation of the neural mechanisms by which arbitrary cues gain motivational salience and, as conditioned reinforcers, control over drug-seeking behaviour. Initially, each infusion of cocaine was made contingent upon a response on one of two identical levers and was paired with a 20-s light conditioned stimulus (CS). Responses on the second lever were recorded, but had no programmed consequence. When rats acquired stable rates of self-administration, a second-order schedule of the type FRx(FRy:S) was introduced, with values of "x" being increased progressively to 10 and then "y" from 2 through 8. Priming (i.e. non-contingent) infusions of cocaine were never given. Once the first infusion was obtained under the second-order schedule, further infusions were made contingent on each response (to a maximum of ten infusions/day). Each stage was repeated daily until the first infusion of each session was achieved within a 5-min criterion. Rats with bilateral, excitotoxic lesions of the basolateral amygdala readily acquired the i.v. self-administration of cocaine under a continuous reinforcement schedule, initially administering more infusions and maintaining a slightly elevated level of self-administration than controls. Despite increased numbers of CS/drug pairings, basolateral amygdala-lesioned rats were severely impaired in the acquisition of the second-order schedule of i.v. cocaine reinforcement. Lesioned rats showed a cocaine dose-response function that was shifted upwards relative to control subjects. There was no significant difference between drug-naive amygdala-lesioned and control animals in the locomotor response to intraperitoneal injections of cocaine. These experiments indicate the feasibility and utility of second-order schedules in studying the neurobehavioural basis of cocaine-seeking behaviour. They suggest a dissociation in the neural mechanisms underlying cocaine-taking and cocaine seeking behaviour, and demonstrate the potential importance of the basolateral amygdala in the processes by which previously neutral stimuli gain control over drug-seeking behaviour.

Amygdala↗
PubMed1995

Differential effects of forebrain 5-hydroxytryptamine depletions on Pavlovian aversive conditioning to discrete and contextual stimuli in the rat.

The experiments examined the effects of depleting forebrain 5-hydroxytryptamine (5HT) on Pavlovian aversive conditioning to discrete and contextual stimuli. Rats were lesioned with intracerebroventricular injections of the neurotoxin 5,7-dihydroxytryptamine and then conditioned in a distinctive environment (termed the context) to a 30 s auditory stimulus. In 50% of animals the interval between the offset of the discrete auditory stimulus and the reinforcer, a mild foot-shock (0.5 mA, 0.5 s), was 5 s (the short-trace group) and in the other 50%, 30 s (the long-trace group). Theory predicts that animals in the short-trace condition will learn more about the discrete stimulus as a predictor of shock and become strongly conditioned, while those in the long-trace condition learn relatively more about the context. The extent of conditioning to the discrete and contextual stimuli was assessed separately, in extinction, using lick-suppression and place-preference measures respectively. Under these conditions sham subjects exhibited the expected dissociation with respect to trace interval. However, lesioned animals exhibited a specific impairment in contextual conditioning. The results are discussed in terms of the behavioural, neurochemical and neuroanatomical specificity of 5HT function in aversive conditioning and the implications for general theories of the role of 5HT in aversive processes.

Animals↗
PubMed1995

The effects of AMPA-induced lesions of the medial septum and vertical limb nucleus of the diagonal band of Broca on spatial delayed non-matching to sample and spatial learning in the water maze.

These experiments investigated in the rat the impact on spatial delayed non-matching to sample and on acquisition of the Morris water maze of (i) AMPA-induced lesions of the medial septal nucleus, which produced a marked reduction of hippocampal choline acetyltransferase activity and acetylcholine levels (measured using in vivo dialysis) together with lesser reductions in cholinergic markers in the cingulate cortex and (ii) similar AMPA-induced lesions of the vertical limb nucleus of the diagonal band of Broca (vDB), which produced more marked reductions in cholinergic markers in the cingulate cortex than in the hippocampus. Medial septal lesions produced a delay-dependent deficit in spatial working memory, while lesions of the vDB resulted in a delay-independent performance deficit. In addition, rats with vDB lesions adopted biased response strategies during the imposition of long delays. Neither lesion significantly affected the acquisition of a spatial reference memory task, the Morris water maze. The results are discussed in terms of cholinergic- and GABAergic-dependent functions of the hippocampal formation and cingulate cortex in spatial short-term and reference memory.

Acetylcholine↗
PubMed1995

The effects of AMPA-induced lesions of the septo-hippocampal cholinergic projection on aversive conditioning to explicit and contextual cues and spatial learning in the water maze.

The environmental context of an animal both subsumes and is associated with the explicit cues that guide its behavioural responses. Recent work in this laboratory suggests that learning about the relationship between the cues which comprise a context depends on the hippocampus. In the present study the role of the cholinergic input to the hippocampus in contextual learning was assessed in rats using a conditioned stimulus/context conditioning paradigm and spatial learning in the Morris water maze. In the former, a place preference apparatus provided the context. The subject was confined in the black chamber and a 'clicker' conditioned stimulus was presented five times in a 20 min period. A trace interval of 5 or 30 s, depending on the group, was interposed between the end of the clicker and a footshock. Theory predicts that animals in the 5 s condition will learn more about the clicker as a predictor of shock and become strongly conditioned, while those in the 30 s condition learn relatively more about the context. Conditioning to the clicker (conditioned stimulus) was measured in a separate lick suppression chamber--presentation of the clicker suppresses drinking, and contextual learning was determined by recording the time spent on the black side of the place preference apparatus when both the black and a familiar white chamber were accessible. Lesions of the medial septum/diagonal band induced by RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) enhanced contextual learning in this paradigm but disrupted conditioned stimulus conditioning in the 30 s condition. Acquisition of the Morris water maze was largely unimpaired. The results are suggested to reflect a shift towards the use of hippocampal-dependent contextual learning strategies in lesioned animals.

Acetylcholine↗
PubMed1995

Parcellation of the frontal cortex of the New World monkey Callithrix jacchus by eight neurotransmitter-binding sites.

The most extensive development during primate brain evolution involves the cortex of the frontal lobe, especially its prefrontal region. The distribution of neurotransmitter receptors is unknown in this part of the cortex of New World monkeys. The respective distributions of eight different receptors for the transmitters L-glutamate (L-glu and NMDA), gamma-amino-butyric acid (GABAA), noradrenaline (alpha 1), acetylcholine (M1 and M2) and serotonin (5-HT1 and 5-HT2) were therefore studied in cortical areas of the frontal lobe of the lissencephalic New World monkey, Callithrix jacchus. The results are compared to earlier data on Old World monkeys in order to obtain insight into evolutionary trends at the level of chemical neuroanatomy. Our results indicate that the density and laminar pattern of some receptors change precisely at the cytoarchitectonic boundaries between different cortical areas, while some other receptors do not exhibit measurable changes. For example, the premotor area 6 can be distinguished from prefrontal areas by its high concentration of adrenergic alpha 1 receptors as labelled with [3H] prazosin, with only the cingulate area 24 showing higher values. In other cases, the receptor distribution changes within a cytoarchitectonically homogeneous area. Thus, area 8 can be subdivided into dorsal and ventral regions on the basis of the distribution of GABAA, muscarinic and serotonin receptors. Comparison of these results in a New World monkey with receptor distributions in other primate species reveals much larger interspecies differences in the areas of the frontal lobe than e.g. in the primary visual cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Quantitative receptor autoradiography of eight different transmitter-binding sites in the hippocampus of the common marmoset, Callithrix jacchus.

The regional and laminar distributions of eight different transmitter-binding sites were measured in the marmoset hippocampus by means of quantitative in vitro receptor autoradiography. Receptors for 5-HT1, L-glutamate, N-methyl-D-aspartate (NMDA) and GABAA were similarly distributed. The highest concentrations of these receptors were found in the pyramidal layer of CA1 and the molecular layer of the dentate gyrus. The 5-HT2 receptors showed the highest concentrations in the oriens layer of CA2. The highest concentrations of muscarinic M1 receptors were seen in the pyramidal layer of CA1. Muscarinic M2 receptors were most densely concentrated in the pyramidal layers of CA1, CA2 and CA3. The noradrenergic alpha 1 receptors were most densely packed in the radiatum-lacunosum-molecular layer of CA2 and the molecular layer of the dentate gyrus. Statistically significant co-distributions of serotoninergic, glutamatergic and GABAergic receptors point to possible interactions between these receptor systems in the same hippocampal regions and layers. Comparisons of marmoset distribution patterns for GABAA, NMDA, L-glutamate and 5-HT1 receptors with those in human hippocampi and those of other primates showed similarities between them. Clear differences in the patterns of alpha 1, M1, M2 and 5-HT2 receptors could be seen between marmoset and human hippocampi, indicating a high degree of species specificity in a presumably "conservative" brain region. More similarities, however, could be found between marmoset and human hippocampi than between those of rat and human brains, especially in relation to 5-HT1 and GABAA receptors and L-glutamate-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Analysis of the effects of intra-accumbens SKF-38393 and LY-171555 upon the behavioural satiety sequence.

The outcome of intra-accumbens infusions of the dopamine D1 receptor family agonist SKF-38393 and the D2 receptor family agonist LY-171555 upon measures taken during the behavioural satiety sequence was assessed (0.01 micrograms, 0.1 micrograms, 1.0 micrograms in each case). Each drug was infused either separately, or together as a co-infusion in order to examine the functional relationship between these dopamine receptor subtypes within the nucleus accumbens. Measures of feeding did not change following infusions of SKF-38393 or LY-171555, whether infused separately or together. However, following separate infusion of the lowest dose tested of each drug (0.01 micrograms), the onset of resting was advanced. Moderate to high doses of SKF-38393 and LY-171555 (0.1 micrograms, 1.0 micrograms) infused separately resulted in a marked increase in activity at the expense of resting. Co-infusion of 0.01 micrograms of each drug also resulted in a dramatic increase in activity. Thus, measures of feeding behaviour were unchanged following excitation of D1 and D2 dopamine receptor families within the nucleus accumbens. In marked contrast, locomotor behaviour appeared to be under the potent synergistic control of these receptor families.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Reversal of visual attentional dysfunction following lesions of the cholinergic basal forebrain by physostigmine and nicotine but not by the 5-HT3 receptor antagonist, ondansetron.

To investigate further the cholinergic specificity of the effects of basal forebrain lesion-induced disruption of attentional performance, the present study examined the efficacy of various pharmacological agents in improving performance of a five-choice serial reaction time task in rats that had received lesions of the cholinergic basal forebrain. Specifically, the effects of the novel 5-HT3 receptor antagonist, ondansetron (0.3, 1, 10 ng/kg), and of nicotine (0.03, 0.06, 0.1, 0.3 mg/kg) and the anticholinesterase, physostigmine (0.05, 0.1 mg/kg), on attentional function were examined in animals which had received AMPA-induced lesions of the nucleus basalis magnocellularis (nbM). The behavioural impairments observed immediately following the lesion were a reduction were choice accuracy and an increase in correct response latency. Although these impairments showed recovery over the course of the following weeks, the deficit in choice accuracy could be reinstated by reducing the duration of the visual stimulus and thus increasing the attentional load placed on the animals. This reduction in choice accuracy could be dose dependently improved by systemic administration of either physostigmine or nicotine, suggesting that this impairment in attentional function may be attributed to disruption of cholinergic function. The pharmacological specificity of these improvements was supported by the inability of d-amphetamine to improve task performance (0.2, 0.4, 0.8 mg/kg). Ondansetron was also unable to improve accuracy of performance in lesioned animals, but was effective in reducing the anticipatory or premature responding observed in both control and lesioned animals, even when elevated (in the case of controls) by treatment with systemic d-amphetamine. The results of the present study therefore suggest that cholinergic dysfunction can lead to attentional impairments which can be ameliorated by cholinergic treatments such as physostigmine and nicotine, but that ondansetron, despite its proposed ability to release cortical acetylcholine, was unable to restore choice accuracy at the doses employed. The results further suggest a double dissociation of effects on accuracy and the disinhibition of responding.

Amphetamine↗
PubMed1995

Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion on focused attention and attentional search.

As the catecholamines have long been implicated in attentional processes, the present investigation compared the effects of the mixed alpha 1/alpha 2 adrenoceptor agonist clonidine (CLO), the benzodiazepine diazepam (DZP), the D1/D2 antagonist haloperidol (HAL) and a low-tryptophan drink (Lo-TRP) on performance of tests of selective attention with distractors in four groups of young, healthy volunteers. Using a placebo-controlled, cross-over design, selective and dissociable effects on performance were found with each pharmacological manipulation. Specifically, CLO acted to broaden the focus of attention, HAL generally slowed reaction times during attentional search, and DZP and Lo-TRP produced differential effects on stimulus-response compatibility during attentional search. Furthermore, these results underline the usefulness of employing a single test with several neurochemical manipulations, allowing for a comprehensive analysis of the neurochemical basis of attention.

Adult↗
PubMed1995

Contrasting effects of clonidine and diazepam on tests of working memory and planning.

The alpha 2 adrenoceptor has recently been implicated in working memory (WM), a function dependent on the integrity of the prefrontal cortex. Using a double-blind, placebo-controlled design, the present investigation examines the effects of two doses (1.5 micrograms/kg and 2.5 micrograms/kg) of the mixed alpha 1/alpha 2 adrenoceptor agonist clonidine (CLO) on performance of various computerised tests of WM and planning in healthy, young volunteers. These are compared to the effects produced by two doses (5 mg and 10 mg) of diazepam (DZP) on largely the same set of neuropsychological tests in a comparable set of subjects. Administration of CLO resulted in impulsivity of responding in a planning task, as well as differential dose-dependent effects on two analogous tests of spatial and visual WM. The nature of these effects were suggestive of mnemonic, rather than executive, dysfunction. Conversely, DZP produced specific deficits on tests of spatial WM and planning very similar to those seen following lesions to the frontal lobes. Therefore, these two sedative drugs produce doubly dissociable, dose-dependent effects on different aspects of cognitive function.

Adult↗
PubMed1995

Clonidine and diazepam have differential effects on tests of attention and learning.

The noradrenergic system has repeatedly been implicated in the mediation of attentional processes. Using a double-blind, placebo-controlled design, the present investigation examines the effects of two doses (1.5 micrograms/kg and 2.5 micrograms/kg) of the alpha 2 adrenoceptor agonist clonidine (CLO) on performance of various computerised tests of attention and learning in healthy, young volunteers. These are compared to the effects produced by two doses (5 mg and 10 mg) of diazepam (DZP) on largely the same set of neuropsychological tests in a comparable set of subjects. Both doses of CLO were found to impair performance of the RVIP test of sustained attention, while the higher dose alone improved visuo-spatial learning. Conversely, the higher dose of DZP produced profound deficits on visuo-spatial learning, and impaired attentional set-shifting. This study suggests a role for the alpha 2 adrenoceptor in selective attention, and for the benzodiazepine receptor in specific cognitive processes mediated by discrete cortical regions.

Adult↗
PubMed1995

Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man.

Three groups of neurosurgical patients with temporal lobe excisions, frontal lobe excisions or unilateral amygdalo-hippocampectomy were assessed on a computerized battery of tasks designed to investigate visuo-spatial short-term recognition memory and learning. A double dissociation is reported between deficits of pattern recognition memory and spatial recognition memory which were observed in the two posterior groups and frontal lobe patients, respectively. In addition, both the temporal lobe and amygdalo-hippocampectomy patients were also impaired on a delayed matching-to-sample paradigm whilst frontal lobe patients performed at an equivalent level to controls. Finally, whilst the impaired performance of the three groups was indistinguishable on a test of paired-associate learning, quite different patterns of deficit were observed on a test of spatial working memory. These results are discussed with reference to recent suggestions that visual recognition memory is mediated by a neural system which includes, as major components, the inferotemporal cortex, the medial temporal lobe structures and particular sectors of the frontal lobe, and are compared to previous findings from patients with idiopathic Parkinson's disease and dementia of the Alzheimer type.

Adult↗
PubMed1995

Neuropsychological evidence for frontostriatal dysfunction in schizophrenia.

Schizophrenics and controls were compared on a computerized test of attentional set-shifting which provides a componential analysis of the Wisconsin Card Sort Test and has previously been shown to be sensitive to frontal lobe dysfunction and Parkinson's disease. The main test was of extra-dimensional shifting where subjects are required to shift response to an alternative perceptual dimension. In one condition, termed 'perseveration', subjects are required to shift to a novel dimension and ignore the previously relevant one. In the other condition, termed 'learned irrelevance', subjects are required to shift to the previously irrelevant dimension and ignore a novel one. Chronic medicated schizophrenics (N = 32) show a highly significant impairment on the perseveration but not the learned irrelevance condition, as compared to normal age and IQ matched controls (N = 24). This was true even of a subgroup of patients with preserved IQ. The impairments in attentional set-shifting failed to correlate with patients' scores on the Mini-Mental State Examination (mean; S.D. 26.8; 1.8) or with scores on a test of recognition memory. These results provide evidence for a specific deficit in a set-shifting test of executive function and support a hypothesis of frontostriatal dysfunction in schizophrenia.

Adult↗
PubMed1995

Comparison of executive and visuospatial memory function in Huntington's disease and dementia of Alzheimer type matched for degree of dementia.

Groups of patients with Hungington's disease and probable dementia of Alzheimer type (DAT) matched for level of dementia on the basis of mini mental state examination scores were compared in several tests of visual memory and tests sensitive to frontal lobe dysfunction. Whereas recall of patients with DAT tended to be worse on the Kendrick object learning test, the two groups were equivalent on tests of sensorimotor ability and delayed matching to sample performance. By contrast, the patients with Huntington's disease were significantly worse on tests of pattern and spatial recognition, simultaneous matching to sample, visuospatial paired associates, and on three tests sensitive to frontal lobe dysfunction--namely, the Tower of London test of planning, spatial working memory, and a visual discrimination learning and reversal paradigm. The impairments in these tests, however, did not always qualitatively resemble those seen in patients with frontal lobe damage and may be more characteristic of primary neostriatal deficit. In the visual discrimination paradigm the patients with Hungtington's disease were significantly worse than the patients with DAT at the simple reversal stage, where they displayed significant preservation to the previously rewarded alternative. The results are consistent with the hypothesis that patients with Huntington's disease exhibit deficits in tests sensitive to frontostriatal dysfunction and that this form of intellectual deterioration is qualitatively distinct from that seen in Alzheimer's disease.

Aged↗