Biomedical subjects

H J Cassaday

Publications and source records attributed to H J Cassaday.

14 recordsLinked to original sources

PubMed2005

Electrolytic lesions to nucleus accumbens core and shell have dissociable effects on conditioning to discrete and contextual cues in aversive and appetitive procedures respectively.

The nucleus accumbens (n. acc.) has been implicated in conditioning to both discrete and contextual cues but its precise role is as yet controversial because conflicting patterns of effect have been reported. These inconsistencies may relate to the extent to which the lesions used encroach on different subfields of n. acc. and the use of different task variants. The present study compared the effects of selective lesions of shell and core subfields of nucleus accumbens (n. acc.) across aversive and appetitive trace conditioning variants. In both experiments, an auditory stimulus was contiguous with footshock or food, or presented at a trace interval. A continuous flashing light in each case provided an experimental background stimulus. Conditioning to the cues provided by the experimental chambers was also assessed. Rats with electrolytic lesions to the n. acc. shell and core showed different patterns of effect in aversive (Experiment 1) and appetitive (Experiment 2) variants of this procedure. In Experiment 1, the core lesion reduced the difference between trace and contiguously conditioned groups, in responding to the discrete noise stimulus. However, neither lesion had any detectable effect on contextual conditioning. In Experiment 2, the shell lesion clearly increased contextual conditioning, selectively in the trace conditioned group, but neither lesion had any detectable effect on discrete cue conditioning. Thus, whilst the shell and core lesions produced dissociable effects on discrete cue and contextual conditioning, the conclusions to be drawn depend on the procedural variant in use.

Animals↗

PubMed2004

CER to discrete and contextual stimuli: effects of stimulus modality depend on strain of rat.

Strain differences in perception, cognition and affect have been found to interact with the effect of experimental treatments on learning. The present study tested Dark Agouti (DA) and Wistar rats in conditioning to discrete and contextual stimuli, for strain differences in conditioned emotional response (CER) and effects of stimulus modality. A Pavlovian trace-conditioning procedure was used in which a discrete target stimulus (flashing light or tone, counterbalanced across groups) was paired either contiguously or at a 30-s trace with footshock. Contextual conditioning was assessed using a background (continuously presented) experimental stimulus (alternate to that used as target). Experiment 1 used 5 x 0.5 mA, 0.5-s footshock and Experiment 2 used 2 x 0.5 mA, 1-s footshock. In both experiments, conditioning to the discrete (target) and background stimuli interacted with strain of rat and stimulus modality. For conditioning to the target stimulus, the trace-conditioning effect (of relatively greater suppression in contiguously conditioned than trace-conditioned groups) differed by stimulus and strain. It was greater for the Wistar strain with the flashing light stimulus and for the DA strain with the click stimulus (although the latter was not significant in Experiment 1). In addition, suppression to the background stimulus was affected by stimulus modality for the DA but not Wistar strain in both experiments. DAs conditioned more to the click than the light as background, whereas there was no difference by stimulus modality for Wistars, although the exact pattern of how this stimulus modality effect was mediated differed between experiments. These results demonstrate that stimulus modality can be an issue when considering apparent strain differences in conditioning.

Acoustic Stimulation↗

PubMed2004

Disruption of latent inhibition to a contextual stimulus with systemic amphetamine.

This experiment examined the effects of 0.5 and 1.5 mg/kg doses of amphetamine (AMP) in male Wistar rats, on conditioning to a contextual stimulus that for half the animals has been pre-exposed, in an appetitive conditioning procedure. Amphetamine was administered during both pre-exposure (3 days) and acquisition (15 days). Latent inhibition (LI, reduced conditioning in pre-exposed relative to non-pre-exposed rats) was seen in controls but not at either AMP dose. This abolition of LI was seen under AMP at two levels of responding in acquisition and confirmed in drug free extinction. It suggests that, like conditioning to discrete stimuli, conditioning to contextual stimuli is subject to LI and can be disrupted by AMP.

Amphetamine↗

PubMed2004

Amphetamine decreases the expression and acquisition of appetitive conditioning but increases the acquisition of anticipatory responding over a trace interval.

The effects of amphetamine on selective learning were tested in a trace conditioning procedure, in which the informativeness of the conditioned stimulus (CS) (noise) was manipulated through the introduction of a time interval before the delivery of the unconditioned stimulus (UCS) (food). The results showed that d-amphetamine (0.5 and 1.5 mg/kg) impaired both the expression (Experiment 1b) and acquisition (Experiment 2) of appetitive conditioning. This was true for both trace and contiguously conditioned groups. The effects of the 0.5 mg/kg dose of d-amphetamine were not attributable to general motor (measured pre-CS) or motivational (measured post-UCS) effects of the drug. Moreover, the same pattern of effects (impaired appetitive conditioning, irrespective of the trace interval between CS and UCS) was confirmed in drug-free extinction tests. By contrast to the general depression in the acquisition and expression of associative learning observed under amphetamine, the 0.5 mg/kg dose promoted the acquisition of anticipatory responses made later in the trace interval (in Experiment 2 but, again, not the expression of previous conditioning in Experiment 1b). This suggests a dissociable effect of low-dose d-amphetamine on learning about the temporal relationship between CS and UCS.

Acoustic Stimulation↗

PubMed2003

Amphetamine increases aversive conditioning to diffuse contextual stimuli and to a discrete trace stimulus when conditioned at higher footshock intensity.

Amphetamine can increase conditioning to poor predictors of reinforcement in selective learning tasks (e.g. latent inhibition, LI). In the present study, a noise stimulus was contiguous with footshock or presented at a trace interval. A flashing light background stimulus was used to measure contextual conditioning. Experiment 1 used 1.5 mg/kg and 6 mg/kg dl-amphetamine. Experiments 2 and 3 used 0.5 mg/kg and 1.5 mg/kg d-amphetamine. Unconditioned stimuli parameters (intensity, number, duration) were also manipulated from one experiment to the next. Amphetamine consistently increased conditioning to the background stimulus, and increased conditioning to the trace stimulus at higher footshock intensity (Experiment 3). Thus, amphetamine increased conditioning only to relatively uninformative predictors. The effect on conditioning to trace conditioned stimuli depended on the level of reinforcer but increased conditioning to background did not. Throughout, there was no effect of amphetamine on conditioning of the contiguous stimulus. Thus, the results did not simply arise because amphetamine increased conditioning under any condition in which conditioning without amphetamine was poor. The results are discussed in terms of amphetamine effects on breadth of attention and LI to context.

Amphetamine↗

PubMed2003

The effect of stimulus height on visual discrimination in horses.

This study investigated the effect of stimulus height on the ability of horses to learn a simple visual discrimination task. Eight horses were trained to perform a two-choice, black/white discrimination with stimuli presented at one of two heights: ground level or at a height of 70 cm from the ground. The height at which the stimuli were presented was alternated from one session to the next. All trials within a single session were presented at the same height. The criterion for learning was four consecutive sessions of 70% correct responses. Performance was found to be better when stimuli were presented at ground level with respect to the number of trials taken to reach the criterion (P < 0.05), percentage of correct first choices (P < 0.01), and repeated errors made (P < 0.01). Thus, training horses to carry out tasks of visual discrimination could be enhanced by placing the stimuli on the ground. In addition, the results of the present study suggest that the visual appearance of ground surfaces is an important factor in both horse management and training.

Animals↗

PubMed2000

Rapid visual learning in the rat: effects at the 5-HT1a receptor subtype.

The 5-hydroxytryptamine1a (5-HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 0.15 mg/kg) impaired rats' rapid visual learning on a computerized maze. This treatment also increased decision time (DT) but the learning impairment was not necessarily a side-effect of slower responding because, in this task, responses made at long DT are more accurate than those at short DT. The selective 5-HT1a receptor antagonist WAY-100635 (0.3 mg/kg) was itself without effect on accuracy, but was effective in reversing effects of 8-OH-DPAT (on both accuracy and DT). Within problems (i.e., over the 40-60 trials of a single discrimination), performance was reduced by treatment with 8-OH-DPAT at all stages of learning. We conclude that this effect is mediated through the 5-HT1a receptor site (rather than through some other serotonergic receptor site or non-specific mechanism) as it was reversible by treatment with WAY-100635. Although it could still arise from behaviourally non-specific effects, the performance deficit finds its best account in terms of the psychological processes necessary to visual learning. Its reversal with WAY-100635 offers support to the hypothesis that 5-HT1a receptor antagonists could improve cognitive function, under conditions of pre-existing impairment due to overactive serotonergic inhibition, as is thought to occur in Alzheimer's disease.

Analysis of Variance↗

PubMed1999

The Gulf War and illness by association.

The symptoms of Gulf War Syndrome (GWS) closely correspond to the physiological and behavioural sequelae of an interleukin-1 (IL-1) mediated sickness response. We propose that this response can account for the variability in its symptomatology. Furthermore, the persistence of GWS can be accounted for by an associative process, whereby the smells/tastes of war become linked with the physiological reaction to environmental stressors encountered in the Gulf and/or the 'cocktail' of drugs given to the soldiers. As required, the IL-1 response is conditionable.

Adaptation, Physiological↗

PubMed1997

The hippocampus, objects, and their contexts.

Rats with hippocampal aspiration lesions and controls were trained on delayed nonmatching to sample with small complex goal boxes, presented trial uniquely. A series of experiments then used pairs of large or small boxes, presented repeatedly. The lesions impaired choice accuracy when the rats were tested with large empty boxes but not when small boxes containing 3-dimensional objects were used. There was a comparable impairment when the rats were tested with pairs of large complex boxes, which contained arrays of objects, identical to those used in the smaller boxes but necessarily spaced further apart. Subsequent experiments revealed that the lesion deficit with large boxes was reduced by insertion of a continuous line of distinctive objects and eliminated by trial-unique presentation of large boxes. The results are discussed in terms of (non) spatial accounts of hippocampal function and the compensatory effects of novel object cues. We conclude that, for hippocampal rats, spatial cues, although useless, can nonetheless be profoundly disruptive.

Animals↗

PubMed1995

Both electrolytic and excitotoxic lesions of nucleus accumbens disrupt latent inhibition of learning in rats.

Evidence indicating a role for the nucleus accumbens in the development of latent inhibition of learning has accumulated. Two experiments were conducted using Wistar rats to investigate this role directly. Experiment 1 used a conditioned emotional response paradigm to assess the effects of discrete electrolytic lesions in the shell region of the nucleus accumbens. Latent inhibition was attenuated by this lesion. In order to determine the contribution made by damage to fibers en passage associated with electrolytic lesions, Experiment 2 assessed the effects of NMDA-induced lesions in the shell of the nucleus accumbens in the same task. Latent inhibition was again significantly attenuated. These findings support the proposition that an intact nucleus accumbens is necessary for the normal development of latent inhibition.

Animals↗

PubMed1995

Fornix-fimbria section and working memory deficits in rats: stimulus complexity and stimulus size.

Rats were trained on delayed matching-to-sample (DMS) with goalboxes containing complex objects as stimuli. On reaching the preoperative learning criterion, the rats were allocated to conventional fornix-lesioned or control groups. In a series of postoperative DMS experiments, different kinds of stimuli were used, ranging from complex object boxes to large, simple black or white goalboxes, with 3 transitional types in between. Lesions impaired choice accuracy whenever the rats were tested with large, simple goalboxes, but not with smaller boxes of otherwise identical construction. A brief, final experiment showed no amelioration of the lesion-induced impairment when complex objects were added to large, simple goalboxes. The results are discussed in terms of spatial and nonspatial accounts of hippocampal function.

Animals↗

PubMed1993

5,7-Dihydroxytryptamine lesions in the fornix-fimbria attenuate latent inhibition.

When animals are preexposed to a stimulus without consequence they are subsequently slower to associate this stimulus with an important event, such as footshock. This retarding effect of stimulus preexposure is called latent inhibition and can be demonstrated in a variety of classical and instrumental paradigms and in a wide range of species, including man. Latent inhibition is disrupted in acute schizophrenics and by amphetamine treatment in both rat and man. The present study investigated the role of hippocampal 5HT terminals in latent inhibition using a conditioned suppression procedure with male Sprague-Dawley rats. Microinjections of 5,7-dihydroxytryptamine in the fornix-fimbria significantly reduced hippocampal indoleamine levels and attenuated latent inhibition of conditioned suppression. This finding supports the hypothesis that the destruction of mesolimbic 5-hydroxytryptamine terminals reduces latent inhibition. This result is discussed in terms of the possible involvement of reduced serotonergic function in schizophrenic attentional disorder. In addition to the predicted lesion effect, biochemical analyses indicated that experimental treatments in the latent inhibition procedure altered neurotransmitter turnover: utilization ratios for 5-hydroxytryptamine and/or dopamine were increased in preexposed relative to nonpreexposed animals in four of the six brain regions sampled.

5,7-Dihydroxytryptamine↗

PubMed1993

Critical determinants of nonspatial working memory deficits in rats with conventional lesions of the hippocampus or fornix.

Rats with conventional lesions of the hippocampus or fornix were compared postoperatively with controls on nonspatial memory tasks. Neither lesion impaired delayed matching-to-sample (DMS) performance in a discrete-trial task involving "pseudo-trial-unique" complex stimuli. An impairment emerged if a single pair of complex stimuli was used throughout each day's session, and the greatest impairment was obtained with the use of a single pair of less complex stimuli throughout each day's test. Transfer to a continuous DMS task with no explicit intertrial interval produced a different pattern because both lesion and control levels of performance were depressed when two complex stimuli were used repeatedly. A final, separate discrimination learning experiment showed that hippocampectomized rats readily discriminated between the stimuli associated with the greatest lesion-induced DMS deficit. Hippocampal dysfunction thus produces clear deficits on non-spatial memory tasks under appropriate test conditions.

Animals↗

PubMedDate not supplied

Theoretical accounts of Gulf War Syndrome: from environmental toxins to psychoneuroimmunology and neurodegeneration.

Non-specific illness includes a wide variety of symptoms: behavioural (e.g., reduced food and water intake), cognitive (e.g., memory and concentration problems) and physiological (e.g., fever). This paper reviews evidence suggesting that such symptoms can be explained more parsimoniously as a single symptom cluster than as a set of separate illnesses such as Gulf War Syndrome (GWS) and chronic fatigue syndrome (CFS). This superordinate syndrome could have its biological basis in the activity of pro-inflammatory cytokines (in particular interleukin-1: IL-1), that give rise to what has become known as the 'sickness response'. It is further argued that the persistence of non-specific illness in chronic conditions like GWS may be (in part) attributable to a bio-associative mechanism (Ferguson and Cassaday, 1999). In the case of GWS, physiological challenges could have produced a non-specific sickness response that became associated with smells (e.g., petrol), coincidentally experienced in the Persian Gulf. On returning to the home environment, these same smells would act as associative triggers for the maintenance of (conditioned) sickness responses. Such associative mechanisms could be mediated through the hypothalamus and limbic system via vagal nerve innervation and would provide an explanation for the persistence of a set of symptoms (e.g., fever) that should normally be short lived and self-limiting. We also present evidence that the pattern of symptoms produced by the pro-inflammatory cytokines reflects a shift in immune system functioning towards a (T-helper-1) Th1 profile. This position contrasts with other immunological accounts of GWS that suggest that the immune system demonstrates a shift to a Th2 (allergy) profile. Evidence pertaining to these two contrasting positions is reviewed.

Association↗