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T W Robbins

Publications and source records attributed to T W Robbins.

At least 307 records · Page 17Linked to original sources
PubMed1987

The effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on the acquisition and retention of a conditional visual discrimination: implications for cholinergic hypotheses of learning and memory.

The effects of ibotenic acid-induced lesions of the ventral pallidum/substantia innominata region, the dorsal pallidum or both on the acquisition and retention of a conditional visual discrimination have been studied in the rat. Lesions of the ventral pallidum and large lesions of the dorsal and ventral pallidum severely impaired both the acquisition and retention of the conditional discrimination. Dorsal pallidal lesions had similar, but less marked effects. The same lesions also impaired the retention of a passive avoidance task, but had no effect on a conditioned taste aversion. Neurobiological investigations revealed that the lesions destroyed cholinergic neurons in the magnocellular nucleus basalis and caused reductions in cortical choline acetyltransferase activity of about 30-40%. Tract-tracing experiments indicated that the lesions destroyed, in particular, cholinergic neurons projecting to the frontal dorsolateral cortex and also those projecting to more posterior cortex, but not the occipital lobes. Contingency analysis of the behavioural, neurochemical and neuroanatomical data indicated that those animals with the largest decreases in choline acetyltransferase activity, or the largest areas of neuronal loss in the ventral and dorsal globus pallidus, were most impaired in the retention of the conditional discrimination. The results do not, therefore, indicate a simple relationship between cholinergic neuronal loss and the retention of response rules essential for performance of the task ("reference memory"). The relevance of the results to cholinergic hypotheses of learning and memory is discussed.

Animals↗
PubMed1987

Dissociable effects of lesions to the dorsal or ventral noradrenergic bundle on the acquisition, performance, and extinction of aversive conditioning.

In six experiments we studied the effects of lesions to either the dorsal or ventral noradrenergic bundle on the acquisition and extinction of the conditioned emotional response (CER) as measured in a conditioned suppression paradigm. Infusions of the neurotoxin 6-hydroxydopamine (6-OHDA) into the trajectory of the dorsal noradrenergic ascending bundle (DNAB) impaired the acquisition of on-the-baseline and off-the-baseline conditioned suppression. The acquisition impairment for on-the-baseline conditioning was also shown to still be present when training did not commence until 8 weeks following central noradrenergic depletion. However, in rats previously trained on the CER, DNAB lesions did not affect performance. There was also a small resistance to extinction following on-, but not off-the-baseline conditioning. The acquisition impairment was shown not to be because of an altered sensitivity to the footshock. In contrast, infusions of 6-OHDA into the ventral noradrenergic ascending bundle (VNAB) had no effect upon the acquisition of the CER in an on-the-baseline procedure, but retarded its extinction to a much greater extent. The results here are discussed in terms of other acquisition deficits shown by rats with DNAB lesions, and with reference to Gray's "anxiety" and Mason's "selective attention" theories of locus coeruleus function.

Animals↗
PubMed1986

The effects of d-amphetamine, alpha-flupenthixol, and mesolimbic dopamine depletion on a test of attentional switching in the rat.

A test of attentional switching was devised for the rat in which it obtained sucrose reinforcement by an appropriate nose-poke response that discriminated which of two visual events terminated first, in a specially designed chamber. The effect of mesolimbic dopamine depletion (to 20% of control values) produced by infusions of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens (N. Acc) on stable discrimination was measured alone and in the presence of a range of doses of d-amphetamine (0.4-2.3 mg/kg IP). The 6-OHDA lesion of the N. Acc impaired postoperative performance transiently by reducing choice accuracy and slowing response latency. By post-operative days 12-16, however, performance recovered to control levels and was not differentially affected by a manipulation of task difficulty. d-Amphetamine produced dose-dependent performance impairments, which were antagonised by the 6-OHDA treatment. In a second group of N. Acc lesioned rats, the neuroleptic alpha-flupenthixol (0.1-1.0 mg/kg) led to fewer trials being completed and longer latencies than in the sham-operated control group. The results are discussed in terms of the possible attentional mechanisms underlying the d-amphetamine-induced disruption of performance mediated by the N. Acc and of the implications for psychopathology resulting from possible dysfunction of this region.

Animals↗
PubMed1986

6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbens d-amphetamine.

Intra-accumbens d-amphetamine enhances responding for reward-related stimuli (conditioned reinforcers, CRs), whereas intra-caudate d-amphetamine has only weak and variable effects (Taylor and Robbins 1984). The present experiment further examined the involvement of the nucleus accumbens and the role of dopamine (DA) in this effect. Thirsty rats were trained to associate a flash of a light and movement of a dipper (CR) with water. After implantation of permanent guide cannulae aimed at the nucleus accumbens, they were assigned to one of four groups, receiving either bilateral 6-OHDA (4 mg/ml free base in 2 microliters 0.1% ascorbic acid/0.9% saline) or sham (vehicle) infusions into the nucleus accumbens or the caudate nucleus. In the test phase, two novel levers were available. Responding on one lever (CR lever) produced the light and dipper stimuli without water presentation, whereas responding on the other (NCR lever) had no effect. All four groups received four counterbalanced intra-accumbens infusions of d-amphetamine (3, 10, 20 micrograms/2 microliters) or vehicle. On the 5th test day, subjects were pretreated subcutaneously with apomorphine (0.1 mg/kg). Intra-accumbens d-amphetamine in both sham-lesioned groups produced a dose-dependent increase in responding on the CR lever, but no significant change on the NCR lever. No selective increases in responding on either lever were found in animals with 6-OHDA-induced depletion of DA (greater than 80%) in the nucleus accumbens following intra-accumbens d-amphetamine; however, in subjects with DA depletion of the posterior caudate nucleus (greater than 80%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Role of central noradrenaline neurons in the contextual control of latent inhibition in taste aversion learning.

Three experiments were performed to examine the effects of noradrenaline (NA) depletion, using 3 different methods: lesions of the dorsal noradrenergic bundle (DB) with 6-hydroxydopamine (6-OHDA), lesions induced by neonatal treatment with 6-OHDA and lesions induced by systemic DSP4 upon latent inhibition, using the taste-aversion learning procedure. NA depleted and control (sham, vehicle or saline) rats were given pre-exposure trials to either novel saccharin or to novel saccharin in a novel type of drinking bottle (the noisy bottle). Later, during conditioning trials saccharin was presented in the noisy bottles for all the rats, followed by lithium chloride injections. Saccharin aversions, tested for in the noisy bottles, indicated considerably weaker saccharin aversions (i.e. more latent inhibition) by the control groups pre-exposed to both saccharin and the noisy bottles. These context-dependent latent inhibition effects were clearly attenuated by all 3 treatments that depleted central NA. Biochemical assays confirmed the NA depletions in each case. The results, demonstrating the intimate role of central NA neurons in contextual control of latent inhibition in taste-aversion learning, appear to conform with current attentional theories of NA function in the forebrain.

Animals↗
PubMed1985

The effects of d-amphetamine, chlordiazepoxide and alpha-flupenthixol on food-reinforced tracking of a visual stimulus by rats.

Rats were trained to respond to one of two levers under a random ratio schedule of food reinforcement. Which of the levers was correct was redetermined before each response and signalled by a light. The effects of d-amphetamine (0.2-3.2 mg/kg), chlordiazepoxide (1-8 mg/kg), and the neuroleptic alpha-flupenthixol (0.03-0.33 mg/kg) on the efficiency of rats tracking this visual cue were examined. d-Amphetamine increased the proportion of responses made on the correct lever at low and intermediate doses, but reduced the proportion at 3.2 mg/kg. At the highest dose, chlordiazepoxide produced a small increase in this measure, together with a reduction in response rate, but alpha-flupenthixol had no effect, even at a dose reducing response rate. Low doses of amphetamine also increased switching between the levers, producing a proportionately greater increase in switching from the correct lever to the incorrect lever than vice versa. The results are interpreted as showing that d-amphetamine facilitates tracking performance as a result of its action of enhancing response switching, and supporting the hypothesis that facilitation of performance by amphetamine-like drugs depends on the effect of the drug on response output coinciding with task requirements.

Animals↗
PubMed1985

Comparative effects of infusions of 6-hydroxydopamine into nucleus accumbens and anterolateral hypothalamus induced by 6-hydroxydopamine on the response to dopamine agonists, body weight, locomotor activity and measures of exploration in the rat.

Groups of rats received infusions of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens or anterolateral hypothalamus with 6-hydroxydopamine (6-OHDA), or sham operations. Body weight was monitored for 28 days after the infusion, after which rats were first tested in an exploration choice-box and then underwent a series of pharmacological challenges. At this time after the operation, rats which had received 6-OHDA in the nucleus accumbens showed neither loss of body weight, deficit in exploration, nor hypokinesia, but sustained an 80% reduction in dopamine levels in the nucleus accumbens. Locomotion was decreased in response to 1.5 mg/kg (i.p.) of d-amphetamine but increased following 0.1 mg/kg (s.c.) of apomorphine; stereotyped responses to larger doses were unaltered. By contrast, rats which had received 6-OHDA in the anterolateral hypothalamus lesions lost substantial amounts of body weight and were hypoactive. Although both locomotor and stereotypy responses to d-amphetamine were abolished, these responses were enhanced in response to apomorphine. Consistent with this, regional assay using high pressure liquid chromatography (HPLC) showed profound loss of dopamine in the caudate-putamen as well as in the nucleus accumbens and frontal cortex. It seems unlikely that the reductions in exploration previously reported after lesions of the mesolimbicocortical dopamine system at the level of anterolateral hypothalamus induced by 6-OHDA are either behaviourally specific or result solely from depletion of dopamine with the nucleus accumbens and frontal cortex.

Animals↗
PubMed1984

Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens.

Stimulant drugs have been shown to enhance the control over behaviour exerted by stimuli previously correlated with primary reinforcers, termed conditioned reinforcers (CR). Experiment 1 examined the possible neuroanatomical specificity of the enhancement of conditioned reinforcement following intracerebral injections of d-amphetamine. Thirsty rats were trained to associate a light with water. In the test phase, water was no longer presented but the light (CR) was intermittently produced by responding on one of two novel levers. Rats with bilateral guide cannulae aimed at the nucleus accumbens, posterior caudate nucleus, or medio-dorsal nucleus of the thalamus received four counterbalanced microinfusions of d-amphetamine (10, 20, 30 micrograms/2 microliters) or vehicle (control) over 4 test days. There was a dose-dependent selective increase in responding on the lever that produced the light (CR) with intra-accumbens d-amphetamine infusions. Quantitatively similar, but much more variable effects were found with intra-caudate infusions and no effects following intra-thalamic d-amphetamine. Experiment 2 provided evidence that the enhanced control over responding by a CR with intra-accumbens d-amphetamine is behaviourally specific. Three groups of rats received a compound tone--plus--light stimulus that was positively, negatively or randomly correlated with water during training. Intra-accumbens d-amphetamine produced selective increases in responding only if the contingent stimulus had been positively correlated. The results suggest that the nucleus accumbens may play an important role in d-amphetamine's enhanced control over behaviour exerted by conditioned reinforcers.

Animals↗
PubMed1984

Effects of unilateral 6-hydroxydopamine lesions of the caudate-putamen on skilled forepaw use in the rat.

This experiment reports a novel means of measuring the effect of unilateral striatal dopamine (DA) depletion on co-ordinated motor behaviour involving skilled forepaw use in rats. Hungry rats were trained to use their forepaws to remove small food pellets from a moving conveyor belt. Behaviour was scored by counting successful retrievals, attempted retrievals and omissions. The rats were trained to a stable baseline, and the forepaw which they used most accurately was determined over a period of 300 trials. 6-Hydroxydopamine (6-OHDA, 8 micrograms base in 2 microliters vehicle (ascorbic acid/0.9% saline) was injected unilaterally into the head of the caudate nucleus to produce selective DA depletion, either ipsi- or contralateral to the preferred paw. A control group received vehicle alone. There was a significant change in paw use in the 6-OHDA treated rats, but not in the controls, even though accuracy was affected similarly in both sham and lesioned groups. Ipsilaterally injected rats showed increased use of the preferred paw (90% pre-operation to 98% post-operation, while contralaterally injected rats showed reduce use (86% pre-operation to 49% post-operation). These changes appeared on the first day postsurgery and were still present 3 months later.

Animals↗
PubMed1983

Increased weight gain and reduced activity in brown adipose tissue produced by depletion of hypothalamic noradrenaline.

The effects of hypothalamic noradrenaline depletion produced by injection of 6-hydroxydopamine (6-OHDA) into the vicinity of cell bodies of the ventral noradrenergic bundle (VNAB) on weight gain, food intake and brown adipose tissue (BAT) activity (as measured by GDP binding in BAT mitochondria), were examined in rats at two different ages and under two different dietary conditions (chow and chow plus palatable cheese). VNAB lesions enhanced weight gain in the chow plus cheese diet conditions and produced small increases in feeding. These effects were parallelled by reductions in BAT activity in the VNAB group, suggesting a reduced capacity for dietary thermogenesis which may contribute to the significant overweight.

Adipose Tissue, Brown↗
PubMed1983

Increased response switching, perseveration and perseverative switching following d-amphetamine in the rat.

Four experiments examined the effects of d-amphetamine on response switching and perseveration in apparatus allowing a choice of response location. The relative 'cost' of a switch between two response locations and repetitive responding at a single location by rats was manipulated in the various test settings to provide baseline probabilities of switching. d-Amphetamine (0.2-2.3 mg/kg) increased response switching. This effect did not depend on switching being necessary to produce reinforcement and was not explained by increases in locomotor activity, motivational change or randomisation of responding. Further evidence was provided in support of a 'probability-dependency' hypothesis, that the effect of the drug depends in part upon the baseline probability of a response. A measure of perseveration independent of response switching (extra responses made prior to the collection of food) showed that increased switching and increased perseveration occurred in the same situation at the same doses, although perseveration generally occurred at higher doses than increased switching. Therefore the effect of amphetamine on response switching or repetition depends on the dose of drug, the context of the response and its probability of occurrence under control conditions.

Animals↗
PubMed1983

Dissociable effects of d-amphetamine, chlordiazepoxide and alpha-flupenthixol on choice and rate measures of reinforcement in the rat.

The role of reinforcers in influencing choice was studied by use of a schedule that included a random intermixing of reinforced and explicitly non-reinforced components. The just-reinforced response had a high likelihood of being repeated (win-stay), although there was no differential reinforcement for doing so, whereas responses just followed by explicit non-reinforcement had a very low probability of repetition (lose-stay). Non-parametric indices based on the theory of signal detection were used to derive a choice measure of reinforcement which was independent of alterations in average response rate. Treatments with d-amphetamine (0.2-4.5 mg/kg), chlordiazepoxide (0.25-16 mg/kg) and alpha-flupenthixol (0.03-0.6 mg/kg) showed that changes in the choice measure could be dissociated from changes in the response rate. These findings were supported by extinction and satiation tests.

Animals↗
PubMed1983

Contrasting interactions of pipradrol, d-amphetamine, cocaine, cocaine analogues, apomorphine and other drugs with conditioned reinforcement.

The effects of various psychomotor stimulant drugs and drugs outside this class were examined on the efficacy of stimuli previously paired with reinforcement or reward (conditioned reinforcers, CR) in controlling responding. Pipradrol (5-45 mumol/kg), d-amphetamine (1.25-15.0 mumol/kg), and the cocaine analogues WIN 35,428 (0.1-30.0 mumol/kg) and in one of two determinations WIN 35,065-2 (0.1-29.0 mumol/kg) all generally increased responding on a lever providing CR, but did not change or decreased responding on a lever providing no CR (NCR). Cocaine (5-125 mumol/kg) and chlordiazepoxide (3.75-60.0 mumol/kg) had no significant effects. Morphine (3.2-32.0 mumol/kg) and alpha-flupenthixol (0.02-2.0 mumol/kg) generally reduced responding on both levers. Apomorphine (0.1-1.0 mumol/kg) generally increased responding on both levers. Neurochemical data showed that d-amphetamine was generally more potent than pipradrol in its effects on in vitro monoamine uptake and release.

Animals↗
PubMed1983

Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal.

Five experiments examined the effects of destruction of the dorsal noradrenergic bundle (DNAB), arising in the locus coeruleus, both on brightness and spatial visual discrimination, and selective attention. An analogue o Leonard's 5-choice serial reaction task for human subjects was used. Hungry rats were trained to detect brief (0.5 sec) flashes of light presented randomly in one of 5 locations with a fixed intertrial interval of 5 sec, paced by the rat. Correct responses were rewarded with food and incorrect responses punished by time-out (darkness + delay). Following training to high levels of accuracy (80%, with less than 20% errors of omission), rats received either 6-OHDA (4 micrograms/2 microliters) injected bilaterally into the trajectory of the dorsal bundle, or injection of vehicle (0.1% ascorbic acid in 0.9% saline). The 6-OHDA lesion was sufficient to reduce cortical NA by 84%. Performance on both the spatial discrimination and brightness (produced by graded reductions in the brightness of the stimuli) discrimination was unaffected by DNAB lesions. However, the DNAB lesion produced significant decreases in accuracy and increases in omissions when the stimuli were presented at faster, unpredictable rates. In addition, although intense white noise failed to produce differential impairments when presented simultaneously with the visual discriminanda, the DNAB lesion significantly impaired accuracy when the noise was presented immediately prior to, but not overlapping, the onset of the visual stimuli. The implications of this pattern of deficits in performance found following DNAB lesions is discussed in terms of disruptive effects of cortical NA depletion upon mechanisms of selective attention and arousal.

Animals↗
PubMed1983

Changes in body weight and food-related behaviour induced by destruction of the ventral or dorsal noradrenergic bundle in the rat.

Three experiments contrasted the effects of 6-hydroxydopamine-induced lesions of the ventral noradrenergic and dorsal noradrenergic projections, predominantly to hypothalamus and cortex, respectively, upon body weight changes and food-related behaviour in the rat. In general, ventral noradrenergic bundle lesions enhanced weight gain and these effects were exaggerated by the provision of palatable cheese to the standard chow diet. In contrast, lesions of the dorsal noradrenergic bundle produced minor changes in body weight. Associated with the effects of ventral noradrenergic bundle lesions were hyperphagia, enhanced suppression of intake of food adulterated with quinine, (at high concentration), a small attenuation of food neophobia, and enhanced acquisition, but not performance, of the eating response to tail-pinch stimulation. These ventral noradrenergic bundle lesions failed to alter basal activity levels, amphetamine anorexia or the diurnal pattern of eating or activity. In contrast, lesions of the dorsal noradrenergic bundle did not produce either hyperphagia or enhanced rejection of food adulterated with quinine. However, there was a strong attenuation of food neophobia and a retarded acquisition (but unimpaired performance) of eating in response to tail-pinch stimulation. The results are discussed in connection with previous studies of ventral and dorsal noradrenergic bundle lesions, with the effects of ventromedial hypothalamic lesions and with the underlying behavioural and physiological processes that mediate these contrasting effects of different neuroanatomical patterns of central noradrenaline depletion.

Animals↗
PubMed1983

The effects of lesions to ascending noradrenergic neurons on discrimination learning and performance in the rat.

Three experiments examined the effect of central noradrenergic depletion on the acquisition and performance of a temporal discrimination in auditory or visual modalities. In Experiment 1, 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle significantly retarded acquisition compared to a similarly lesioned ventral noradrenergic bundle-group, two sham-operated and one unoperated control group. In Experiment 2, the acquisition impairment produced in the dorsal noradrenergic bundle group was replicated, for both auditory and visual modalities, by lesions depleting hippocampal and neocortical noradrenaline by over 80%. In rats subsequently switched to discriminations involving the unfamiliar modality, the dorsal-bundle lesion also impaired acquisition several weeks after surgery. Experiment 3 showed significantly impaired performance in rats with dorsal bundle lesions when training prior to surgery had not resulted in better than chance performance. In rats previously trained to criterion, the dorsal bundle lesion transiently, but non-significantly, impaired performance. In rats performing better than chance, but not having reached criterion, there were no significant effects of the dorsal bundle lesion. Subsequent manipulations of deprivation and difficulty of discrimination in general failed to distinguish between the dorsal bundle lesion and sham-groups, suggesting that the acquisition impairment did not result from simple sensory or motivational effects. Reducing the interstimulus interval did impair the dorsal bundle group more than controls. However, there was no evidence of altered "distractibility" in the lesioned group when the alternative modality was introduced as a distractor. The results are discussed in terms of other acquisition deficits shown by rats with central noradrenaline depletion and their significance for determining the functions of the projections from the locus caeruleus via the dorsal noradrenergic bundle to the neocortex and hippocampus.

Afferent Pathways↗
PubMed1983

Behavioral and pharmacological specificity of the feeding elicited by cholinergic stimulation of the substantia nigra in the rat.

Microinjections of the cholinergic agonist carbachol into anterior substantia nigra dose dependently increased food intake in satiated rats. This resulted from a prolongation of the duration of eating. In the absence of food, those doses of carbachol that stimulated food intake (.1 and .5 microgram) had no effect on any other response examined, including gnawing, drinking, locomotion, grooming, sniffing, and rearing. The effect of carbachol depended on the degree of prior food deprivation, but supra-additive effects of carbachol and deprivation were not observed. These results are contrasted with those of previous studies demonstrating the nonspecific behavioral effects of electrical stimulation of the brain and of studies showing that carbachol has radically different behavioral effects at other central nervous system sites. Microinjection of an acetylcholine/eserine sulfate mixture also significantly increased food intake. This response was abolished by prior microinjection of the muscarinic receptor antagonist atropine into the substantia nigra, a result that provides evidence for pharmacological specificity of the behavioral effects. These data provide further evidence for the hypothesis that a functional cholinergic system is present within substantia nigra.

Acetylcholine↗