PubMed Health⌕ Search

Biomedical subjects

T W Robbins

Publications and source records attributed to T W Robbins.

At least 235 records · Page 13Linked to original sources
PubMed1993

Cholecystokinin-dopamine interactions within the nucleus accumbens in the control over behaviour by conditioned reinforcement.

Cholecystokinin (CCK) is colocalised with dopamine in the postero-medial nucleus accumbens (NAS). We have utilised an acquisition of a new response procedure to investigate the interaction between CCK and dopamine in the control over behaviour by conditioned reinforcers. A conditioned reinforcer (CR) may be defined as an initially neutral stimulus which gains control over behaviour through selective association with a primary reinforcer. Here, rats learned to associate a light/noise compound stimulus with the imminent availability of 10% sucrose reinforcement. Later, in the absence of sucrose, responding on one of two novel levers (the CR lever) was acquired and maintained by contingent presentation of the CR alone, while responding on the second lever had no programmed consequences. In Expt. 1, infusion of 10 micrograms D-amphetamine within the postero-medial NAS enhanced responding selectively on the CR lever. Infusion of sulphated CCK octapeptide (CCK: 1 or 10 ng) alone within the same area had no effect on response rate. However, infusion of CCK immediately prior to D-amphetamine caused a dose-dependent potentiation of the impact of D-amphetamine upon rates of response on the CR lever. In Expt. 2, infusion of D-amphetamine (10 micrograms) within the postero-medial NAS again enhanced responding selectively upon the CR lever. Intra-accumbens infusion of CCK (10 ng), or s.c. administration of the CCKA receptor antagonist devazepide had no effect upon response rates. However, CCK again potentiated the D-amphetamine-induced increase in rates of response, and this potentiation was blocked by pretreatment with devazepide. These results are discussed in terms of the co-modulation by CCK and dopamine of the processing of reward-related stimuli within the NAS.

Afferent Pathways↗
PubMed1993

Differential effects of intra-accumbens and systemic amphetamine on latent inhibition using an on-baseline, within-subject conditioned suppression paradigm.

Latent inhibition (LI) is a phenomenon in which repeated, non-reinforced presentation of a stimulus retards subsequent conditioning to that stimulus. Several recent experiments have suggested that LI is abolished following acute, low doses of amphetamine given during pre-exposure and conditioning, and this effect has been attributed to amphetamine-induced changes in dopamine levels in the nucleus accumbens. Experiments 1 and 2 examined the effects of two doses of intra-accumbens d-amphetamine (10 micrograms/microliters and 3 micrograms/microliters) on LI in an on-baseline, within-subject conditioned suppression paradigm. There was no effect of either dose on LI, but a significant disinhibition of conditioned suppression resulted in a retardation of learning. In experiment 3 the effects of a low dose of systemic d-amphetamine (0.5 mg/kg) on latent inhibition were examined. The results replicated the abolition of LI found in previous studies, and demonstrated enhanced post-shock suppression in amphetamine-treated animals. These data provide no evidence for the involvement of the mesolimbic dopamine system in LI.

Acoustic Stimulation↗
PubMed1993

Relative roles of ventral striatal D1 and D2 dopamine receptors in responding with conditioned reinforcement.

Several experiments investigated the involvement of D1 and D2 dopamine receptors in the ventral striatum in the control over behaviour by a conditioned reinforcer using an acquisition of new response procedure. Intra-accumbens infusion of either the D1 receptor antagonist, SCH 23390, or the D2 receptor antagonist, raclopride, completely blocked the potentiative effects of intra-accumbens d-amphetamine on responding with conditioned reinforcement and reduced responding to control levels. SCH 23390 was more potent than raclopride. At higher doses in the absence of d-amphetamine, both antagonists also blocked the preference for responding on the lever producing the conditioned reinforcer. Intra-accumbens infusions of either the D1 receptor agonist, SKF 38393, or the D2/3 receptor agonist, LY 171555 (quinpirole), selectively potentiated responding on the lever producing the conditioned reinforcer. Various combined infusions of the D1 and D2 agonists in specific low doses had additive, but not synergistic, effects on responding with conditioned reinforcement. None of the drugs affected the drinking of water in deprived subjects when infused intra-accumbens. These results suggest that both D1 and D2 receptors in the nucleus accumbens are involved in mediating the effects of dopamine in potentiating the control over behaviour by conditioned reinforcers.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Comparative effects of excitotoxic lesions of the hippocampus and septum/diagonal band on conditional visual discrimination and spatial learning.

Several experiments compared the effects of excitotoxic lesions of the septal/vertical limb nuclei of the diagonal band of Broca (VDB) complex with those of the hippocampus (sparing the subiculum) on different forms of visual discrimination learning. The septal/VDB lesions, which produced significant reductions in choline acetyltransferase activity in the hippocampus and the cingulate cortex, impaired acquisition of a conditional visual discrimination in an operant chamber, while the hippocampal lesion had no effect, unless there was a delay interposed between the discriminative stimulus and the response. Neither lesion affected simple visual or spatial discrimination or reversal learning, also carried out in operant chambers, but both significantly impaired the acquisition and retention of a spatial navigation task (Morris water maze), with the septal/VDB lesions again producing greater deficits than the hippocampal lesions. Possible explanations for this surprising result are discussed and it is concluded that; (1) additional cholinergic de-afferentation of the cingulate cortex produced by the septal/VDB lesion is of functional significance; (2) this may lead to deficits in conditional rule learning, which can contribute to spatial navigation performance under certain circumstances; and (3) the contribution of septal-hippocampal cholinergic projections to spatial learning is in need of re-appraisal.

Animals↗
PubMed1993

Visuospatial memory deficits at different stages of Parkinson's disease.

Groups of patients with idiopathic Parkinson's disease (PD), either medicated or unmedicated, were compared with matched groups of normal controls on a computerised battery of tests designed to investigate spatial working memory, visuospatial recognition memory and learning. The medicated PD patients were subdivided into those with mild and severe clinical disability on the basis of Hoehn and Yahr ratings, thus making three groups of PD patients in all. In a test of spatial recognition memory, a significant impairment was only evident in those PD patients who were medicated and had severe clinical symptoms (Hoehn and Yahr stage III-IV). In contrast, none of the three patient groups were impaired in a complementary test of visual pattern recognition memory. Whilst all three patient groups performed well in a test of simultaneous visual matching to sample, medicated patients (MED PD) with severe clinical symptoms were significantly impaired when a short (0-12 sec) delay was introduced. In a test of paired associates learning requiring both visual pattern and visuospatial memory, deficits in learning and memory were only evident in the severely impaired MED PD group. In contrast, in a test of spatial working memory known to be sensitive to frontal lobe damage, significant impairments were found in both groups of medicated PD patients and particularly in those patients with more severe clinical symptoms. Taken together, the results suggest that there are multiple memory impairments in PD which may differentially depend on the clinical severity of the disease.

Aged↗
PubMed1993

Distribution of seven major neurotransmitter receptors in the striate cortex of the New World monkey Callithrix jacchus.

The distribution of seven different binding sites for the transmitters L-glutamate (L-glutamate binding sites and N-methyl-D-aspartate receptor), GABA (GABAA receptor), noradrenaline (alpha 1 receptor), acetylcholine (muscarinic M1 and M2 receptors) and serotonin (5-hydroxytryptamine1 receptor) are analysed in the primary visual cortex (area 17) of the common marmoset, Callithrix jacchus, using quantitative autoradiography. All binding sites show a well-defined laminar pattern, which changes sharply at the cytoarchitectonic border to area 18. The quantitative data show that the distribution of different receptors is relatively invariant across the cortical layers. Almost all receptors show a maximum in supragranular layers, low densities in layers IVA/IVB and a second maximum in layer IVC. Statistical analysis of these similarities in laminar distribution patterns of different receptors (co-distribution) reveals, as in other brain regions and species, that L-glutamate binding sites are co-distributed with N-methyl-D-aspartate, GABAA, and muscarinic M1 and M2 receptors. This may reflect the structural basis of a possible interaction between these receptors and their respective transmitters on the level of single cortical layers. Further co-distributions are found between N-methyl-D-aspartate, GABAA and M1, as well as between alpha 1 and M1 and finally between M1 and M2 receptors. Since not all receptors are co-distributed, the similarities in laminar patterns reveal specific aspects of the neurochemical organization of the cortex when receptors of different transmitter systems are analysed in the same brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of medial dorsal thalamic and ventral pallidal lesions on the acquisition of a conditioned place preference: further evidence for the involvement of the ventral striatopallidal system in reward-related processes.

In our previous work, it has been established that the basolateral amygdala and ventral striatum are part of a neural system that is involved in reward-related processes. However, it is unclear how information processed in this limbic-motor interface may come to affect incentive motivational responses. The present experiments have investigated the involvement of post-striatal elements of the ventral striatopallidal system in the rat. Lesions of the anterior or posterior domains of the ventral pallidum, which receives the major outflow from the ventral striatum, or the nucleus medialis dorsalis of the thalamus, which receives projections from both the ventral pallidum and also the basolateral amygdala, were made by infusing the excitotoxin, ibotenic acid. The effects of the lesions on the acquisition of a place preference conditioned by exposure of hungry rats to sucrose were then measured. Lesions of either the anterior or posterior ventral pallidum significantly attenuated, whereas lesions of the medial dorsal thalamus completely abolished, the acquisition of a conditioned place preference, provided that the latter lesions included the medial-lateral extent of the nucleus. Medial dorsal thalamic lesions did not damage the stria medullaris or medial habenula. Ingestion of sucrose following 23 h deprivation was unaffected by either ventral pallidal or medial dorsal thalamus lesions and thus disruption of place preference acquisition was not secondary to changes in primary motivation. The results indicate that reward-related processes, as measured in the place preference conditioning paradigm, may depend upon ventral striatopallidal outflow that engages medial dorsal thalamus-frontal cortex mechanisms, in addition to the previously highlighted direct outflow to brainstem elements of the motor system.

Amygdala↗
PubMed1993

Contrasting mechanisms of impaired attentional set-shifting in patients with frontal lobe damage or Parkinson's disease.

Tests which assess the ability to shift cognitive set modelled after the Wisconsin Card Sorting Test are particularly sensitive to impairments in patients with Parkinson's disease as well as in patients with frontal lobe damage. However, the underlying mechanisms responsible for the similar deficits observed in the two patient groups are not well understood and may not be identical. For example, an apparent deficit in set-shifting ability may reflect either an impairment in the ability to shift from a perceptual dimension which has previously commanded attention (i.e. 'perseveration'), or in the ability to shift to an alternative perceptual dimension which has previously been irrelevant (i.e. 'learned irrelevance'). In this study, the performance of both medicated and non-medicated patients with Parkinson's disease were compared with a group of neurosurgical patients with localized excisions of the frontal lobes on a novel task designed to assess the relative contribution of 'perseveration' and 'learned irrelevance' to impaired set-shifting ability. Patients with frontal lobe damage were worse than controls in their ability to shift attention from a previously relevant stimulus dimension. Medicated patients with Parkinson's disease were worse at shifting to a previously irrelevant dimension. In contrast to both groups, nonmedicated patients with Parkinson's disease were impaired in both conditions. These results suggest that the gross set-shifting deficits reported in both frontal lobe patients and patients with Parkinson's disease may involve fundamentally different, though related, cognitive processes, and that these may be differentially affected by medication. Specifically, L-dopa therapy may protect Parkinson's disease patients from preservation of attention to a formerly relevant stimulus dimension.

Aged↗
PubMed1993

Memory deficits in Korsakoff and non-Korsakoff alcoholics following alcohol withdrawal and the relationship to length of abstinence.

It has been suggested that both Korsakoff and non-Korsakoff alcoholics share certain memory deficits following alcohol withdrawal. Since both groups have in common long-term alcohol abuse, this has been posited as evidence that alcohol per se can cause irreversible cognitive impairment. This hypothesis has been examined by comparing age and IQ matched groups of detoxified Korsakoff and non-Korsakoff alcoholics and normal controls on pencil and paper and computerised (CANTAB) memory tests. The results indicate that Korsakoff but not non-Korsakoff alcoholics have neuropsychological deficits on tests which have demonstrated medial temporal-lobe/diencephalic dysfunction in humans and non-human primates. Although non-Korsakoff alcoholics showed deficits on the Wechsler Memory Scale subtests these could not be related to damage of specific neuronal systems. Furthermore there was evidence that for the non-Korsakoff but not the Korsakoff alcoholics, superior performance on the Wechsler memory scale subtests was related to increased length of abstinence and independent of either age or duration of drinking.

Adult↗
PubMed1992

Drug discrimination learning in rats with excitotoxic lesions of nucleus basalis and ventral globus pallidus.

Rats can readily acquire conditional discriminations in which mixtures of drugs serve as compound internal discriminative stimuli. Excitotoxic lesions in the region of the nucleus basalis have been shown to impair the acquisition of conditional discriminations based upon external visual stimuli, but nothing was known about their effects on discrimination of internal stimuli. A baseline of undiscriminated bar-pressing for food reinforcers was established prior to surgery. Lesions were made by infusing either ibotenic or quisqualic acid bilaterally into the basal forebrain (the ibotenate-induced lesions had been shown previously to impair cortical cholinergic function and to produce non-specific damage). After surgery, rats were trained to discriminate effects of drug mixtures using a standard, two-bar operant conditioning procedure. The ibotenate, but not the quisqualate, lesion impaired the acquisition of a discrimination of a mixture of (+)-amphetamine plus pentobarbitone, while neither lesion impaired acquisition with a mixture of (-)-nicotine plus midazolam. The ibotenate lesions also reduced overall rates of responding in both experiments. Thus, the deficit in the acquisition of drug discrimination in rats with ibotenate lesions had some pharmacological specificity, but could not be related easily to disturbances in neocortical cholinergic function. In comparisons with other published data, the results suggest a possible dichotomy in the processing of interoceptive and external information in the basal forebrain, a major target of ventral striatal overflow.

Animals↗
PubMed1992

Social isolation increases the density of [125I]omega-conotoxin GVIA binding sites in the rat frontal cortex and caudate nucleus.

Rats were reared from weaning either in isolation or in social groups for 12 weeks. Potential isolation-related changes in L- and N-type voltage-sensitive calcium channels (VSCCs) were assessed by the in vitro binding of [3H]isradipine (100 pM) and [125I]omega-conotoxin GVIA (4 pM) to membranes prepared from three discrete central nervous system regions: frontal cortex, caudate nucleus and hippocampus. The [3H]isradipine binding was generally not affected by isolation. However, [125I]omega-conotoxin GVIA binding was significantly higher in frontal cortex (52%) and caudate nucleus (75%) of isolated rats when compared with socially reared controls. The increased [125I]omega-conotoxin GVIA binding reflected an elevated density of binding sites without an alteration of receptor affinity. The possible contribution of an increased density of neuronal N-VSCCs (as labeled with [125I]omega-conotoxin GVIA) to the behavioral and neurochemical changes observed in 'isolation syndrome' is discussed.

Animals↗
PubMed1992

Attentional functions of the forebrain cholinergic systems: effects of intraventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task.

Degeneration of the cholinergic magnocellular neurons in the basal forebrain and their cortical projections is a major feature of the neuropathology of Alzheimer's disease. In the present study, two experiments examined the disruptive effects on visual attentional performance of two different manipulations that reduce central cholinergic function. In Expt. I, pharmacological manipulation of the cholinergic system was investigated using icv administration of hemicholinium (HC-3), a high affinity choline uptake blocker, administered either alone or in conjunction with the anticholinesterase, physostigmine. The results revealed impairments in the ability of the rats to localize brief visual targets in a serial reaction time task, as shown in particular by a reduction in choice accuracy and lengthening of the latency to respond correctly to the visual stimulus. Cholinergic specificity was supported by the reversal of these behavioural impairments by pre-treatment with the anticholinesterase, physostigmine. In Expt. II, quisqualate-induced lesions of the basal forebrain produced behavioural deficits at 3 weeks post-lesion surgery similar to those observed following icv infusion of HC-3. In an attempt to restore the extrinsic cortical cholinergic innervation by reinnervation of the deafferented cortex, embryonic basal forebrain cholinergic cells were transplanted into the cortex of lesioned animals. After three months recovery, impairments in performance on the baseline schedule of the task were no longer apparent in lesioned animals. However, behavioural deficits, observed predominantly as a lengthening of correct response latency, could be reinstated in the lesioned animals by interpolation of distracting bursts of white noise during each trial, and this deficit was ameliorated by the cholinergic grafts. Furthermore, a non-specific effect of both cholinergic and non-cholinergic grafts in controlling the increase in perseverative time-out responses which occurred as a result of the basal forebrain lesion was consistently observed. These results suggest that cholinergic dysfunction can produce deficits in visual attention which can be ameliorated by cholinergic treatments such as physostigmine or cholinergic-rich cortical grafts. These data provide support for a role for the basal forebrain-neocortical cholinergic projection in attentional function.

Acetylcholine↗
PubMed1992

L-dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction.

A group of ten patients with idiopathic Parkinson's disease (PD) was tested on a series of automated tests of learning, memory, planning and attention whilst either on or off L-dopa medication. Controlled withdrawal of L-dopa interfered with aspects of performance on three of the tests that had previously been shown to be sensitive to frontal lobe dysfunction; a spatial working memory task, the Tower of London planning test, and a visual discrimination paradigm that also included intra- and extra-dimensional shift tests of selective attention. More specifically, errors were increased in the spatial working memory test, and both the accuracy and latency of thinking were impaired. Thinking time was significantly slowed following L-dopa withdrawal, even though the possible contaminating effects on motor slowing were fully controlled by a yoked control procedure. Nine out of ten patients reached a further stage of the visual discrimination, set-shifting paradigm when on, rather than off, L-dopa medication. Spatial span was also impaired off medication, but there were no effects of L-dopa withdrawal on tests of pattern and spatial recognition memory, simultaneous and delayed matching to sample or visuospatial conditional associative learning. Comparisons with a large control group confirmed previous findings that PD is associated with deficits on the majority of these tests. The results are discussed in terms of the fronto-striatal, dopamine dependent nature of some of the cognitive deficits found in PD, but the apparent dopamine-independent nature of deficits in other aspects of cognitive functioning, notably in tests of visual recognition memory and associative learning.

Brain Diseases↗
PubMed1992

Disruptive effects of muscimol infused into the basal forebrain on conditional discrimination and visual attention: differential interactions with cholinergic mechanisms.

The behavioral effects of GABAergic manipulation of the basal forebrain were investigated using two behavioral tasks, which previous studies have shown to yield dissociable effects following quisqualate-induced lesions of the basal forebrain: a five-choice serial reaction time task, involving approaching the location of a brief visual stimulus that is associated with reward; and a conditional visual discrimination task, requiring retrieval of information about a discriminative stimulus that stays constant over time. Following acquisition of the tasks, chronic guide cannulae were stereotaxically implanted into the basal forebrain. Those animals trained on the conditional visual discrimination task showed a dose-dependent reduction in choice accuracy and a lengthening of latency to respond correctly to the visual stimulus following administration of the GABA-A agonist, muscimol (1, 2, 3 ng/microliters/hem). While certain of these deficits, for example response latency, could be restored to control levels by co-administration of the GABA-A antagonist, bicuculline, none of the behavioural impairments could be significantly attenuated by systemic by systemic co-administration of the cholinesterase inhibitor, physostigmine (0.05, 0.1, 0.2 mg/kg, IP). Similarly, a dose dependent effect of muscimol (1, 1.5, 2 ng/microliters/hem) on choice accuracy and correct response latency was observed on performance of the five-choice attentional task. However, in contrast to the conditional task, significant attenuation of the impairment in choice accuracy was obtained following administration of physostigmine (0.05 and 0.1 mg/kg). Attenuation of muscimol-induced deficits by administration of bicuculline was also observed. It is therefore evident that although manipulation of GABAergic activity in the region of the basal forebrain produces profound deficits in different tasks of cognitive function, only some of these may be due to modulation of the magnocellular cholinergic projection to the neocortex.

Animals↗
PubMed1992

Differential effects of mesocortical, mesolimbic, and mesostriatal dopamine depletion on spontaneous, conditioned, and drug-induced locomotor activity.

Groups of rats with 6-hydroxydopamine (6-OHDA) lesions of either the medial prefrontal cortex (PFC), nucleus accumbens (NAC), or caudate putamen (CPu) were given daily tests for locomotor activity in photocell cages while food deprived. Two separate groups of NAC-lesioned rats were prepared with either large [NACT (90% NAC dopamine depletion)] or partial [NACP (67% NAC dopamine depletion)] lesions. NACT rats were spontaneously hypoactive whereas NACP rats were hyperactive compared with sham-operated controls. PFC-lesioned rats were also hyperactive compared to their respective controls. Spontaneous locomotor activity in CPu-lesioned rats did not differ from shams. When daily food supplements were paired with the photocell cages, all subjects developed a conditioned locomotor response. During the first few days of conditioning, the response to this conditioning procedure was markedly greater in the NACP group whereas the response in the NACT group was unaffected initially and actually enhanced during the latter days of testing. The locomotor response to the conditioning procedure was unaffected in either the PFC- or CPu-lesioned groups. Both the NACT and NACP lesions attenuated the locomotor response to 1.5 mg/kg d-amphetamine sulphate IP, and the NACT group showed a supersensitive response to 0.1 mg/kg apomorphine HCl SC. PFC or CPu 6-OHDA lesions did not alter the response to either drug. These results differentiate the role of PFC, NAC, and CPu dopamine in spontaneous, conditioned, and drug-induced locomotor activity and further implicate dopaminergic mechanisms of the NAC in the magnitude of the behavioural response to incentive stimuli.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry.

This series of experiments compared isolation-reared and socially reared rats for their locomotor activity, behavioural stereotypy, and monoamine function both postmortem and in vivo using intracerebral dialysis. In Experiment 1, isolates showed an altered time course of locomotor activity following d-amphetamine sulphate (AMPH) administration (0.5, 2.0, 3.0, or 5.0 mg/kg, SC). Isolation-reared rats also showed increased sensitivity to the sedative effects of a low dose of apomorphine hydrochloride (0.1 mg/kg) but did not differ from social controls following higher doses of the drug (0.5, 1.5, or 3.0 mg/kg, SC). Isolates showed a decrease in the intensity of apomorphine-induced stereotyped behaviours but no change in stereotypy induced by AMPH. In Experiment 2, isolates had higher postmortem dopamine (DA) concentrations and an altered asymmetry in DA function in the medial prefrontal cortex (PFC) but not in the nucleus accumbens (NAC) or caudate putamen (CPu). Isolated rats also had a lower 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the NAC (but not in the PFC or CPu) compared to controls. Experiment 3 used intracerebral dialysis to examine monoamine function in vivo following isolation rearing. Isolates showed greater increases in extracellular DA and greater decreases in DOPAC in response to 2 mg/kg AMPH SC in both the NAC and CPu. There were no apparent differences in the perfusate concentrations of either dopamine (DA), dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) prior to drug administration. However, consistent with the results of Experiment 2, isolates had a reduced basal perfusate concentration of 5-HIAA from the NAC but not from the CPu. Experiment 4 measured postsynaptic DA function in CPu tissue slices following isolation. Isolation rearing did not affect cAMP accumulation in response to stimulation of D1 DA receptors by DA (0, 2.7, 9, or 30 microM). In addition, isolation rearing did not affect the coupling between D1 and D2 receptors, as measured by the increase in cAMP accumulation with 1 microM 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepin (SK&F 38393) and its reduction by 10 microM quinperole hydrochloride (LY 171555). These results are discussed in terms of the possible relationship between these neurochemical findings and the behavioural disturbances following isolation rearing of rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets.

The effects of N-methyl-D-aspartate-induced lesions of the basal forebrain were studied on performance of a series of visual discrimination tests that examined a range of cognitive functions in the marmoset. These included the ability to attend to the various dimensional properties of stimuli and to use just one of these properties in order to solve a discrimination (intra-dimensional shift); to switch attention from one dimension to another (extra-dimensional shift); to learn the reinforcement value of specific exemplars within a dimension (new learning); and to relearn their reinforcement value following reversal of the reward contingencies (serial reversals). Lesions of the basal forebrain did not impair the ability either to attend selectively to the dimensional properties of the stimuli or to switch attention from one dimension to the other. However, the lesion did affect various aspects of associative learning including a transient impairment of new learning and a marked disruption of serial reversal learning. The reversal deficit could be characterised as a tendency to perseverate on the previously correct stimulus and as a failure to to show the formation of a reversal learning set. In addition, the lesion prevented disruption of performance of a well-learned discrimination when novel exemplars from the irrelevant dimension were introduced (probe test). It is suggested that the functional effects of the basal forebrain lesion reflect impaired learning of stimulus-reward associations and behavioural rigidity. The finding, however, that there was no effect of the lesion on attentional set-shifting suggests that any loss of inhibitory control was specific to the level of stimulus-response or stimulus-reward associations, inhibitory control at the level of attentional selection remaining intact. The similarity of the effects of damage to the basal forebrain to those seen following damage to the orbitofrontal cortex and the amygdala are discussed in the context of the close anatomical and functional relationships that exist among these three structures.

Animals↗