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.

Improving laboratory animal science and welfare requires both new scientific research and insights from research in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the ‘3Rs’), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they design research programmes, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on methods employed by other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including on issues around: international harmonisation, openness and public engagement, ‘cultures of care’, harm-benefit analysis and the future of the 3Rs. The process outlined below underlines the value of interdisciplinary exchange for improving communication across different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy.

When animals are exposed to a stimulus that has no consequences they are subsequently impaired in learning that this stimulus predicts an important event, such as footshock. This retarding effect of stimulus pre-exposure is called latent inhibition (LI) and is reliably disrupted by amphetamine, antipsychotics having an opposite effect. The present experiments investigated whether agents which affect serotonergic transmission also attenuate LI, using a conditioned suppression of drinking procedure. The results showed that the 5-HT(2) antagonist ritanserin (2.0 mg/kg), and the 5-HT(1b) agonist RU 24969 (0.5 and 10.0 mg/kg) attenuated LI by increasing learning in pre-exposed animals, whilst the effects of the 5-HT(1a) agonist 8-OH-DPAT (0.38 mg/kg), though in a similar direction, were not significant. These experiments provide partial support for the involvement of serotonin in LI. Since amphetamine-induced attenuation of LI has been proposed as a model for the attentional deficits found in acute schizophrenia, these results are discussed in terms of the possible involvement of reduced serotonergic function in schizophrenic attentional disorder.

Certain types of violent offending are often accompanied by evidence of personality disorders (PDs), a range of heterogeneous conditions characterised by disinhibited behaviours that are generally described as impulsive. The tasks previously used to show impulsivity deficits experimentally (in borderline personality disorder, BPD) have required participants to inhibit previously rewarded responses. To date, no research has examined the inhibition of responding based on Pavlovian stimulusstimulus contingencies, formally 'conditioned inhibition' (CI), in PDs. The present study used a computer-based task to measure excitatory and inhibitory learning within the same CI procedure in offenders recruited from the 'Personality Disorder' and the 'Dangerous and Severe Personality Disorder' units of a high security psychiatric hospital. These offenders showed a striking and statistically significant change in the expression of inhibitory learning in a highly controlled procedure: the contextual information provided by conditioned inhibitors had virtually no effect on their prepotent associations. Moreover, this difference was not obviously attributable to nonspecific cognitive or motivational factors. Impaired CI would reduce the ability to learn to control associative triggers, and so could provide an explanation of some types of offending behaviour.

The muscarinic acetylcholine receptor is an important modulator of medial prefrontal cortex (mPFC) functions, such as the working memory required to bridge a trace interval in associative leaning. Aversive and appetitive trace conditioning procedures were used to examine the effects of scopolamine (0.1 and 0.5 mg/kg, i.p.) in male rats. Follow-up experiments tested the effects of microinfusion of 0.15 μg of scopolamine (0.075 μg of in 0.5 μl/side) in infralimbic (IL) versus prelimbic regions of rat mPFC, in appetitive trace and locomotor activity (LMA) procedures. Systemic scopolamine was without effect in an aversive trace conditioning procedure, but impaired appetitive conditioning at a 2 s trace interval. This effect was demonstrated as reduced responding during presentations of the conditioned stimulus (CS) and during the interstimulus interval (ISI). There was no such effect on responding during food (unconditioned stimulus, US) responding or in the intertrial interval (ITI). In contrast, systemic scopolamine dose-relatedly increased LMA. Trace conditioning was similarly impaired at the 2 s trace (shown as reduced responding to the CS and during the ISI, but not during US presentations or in the ITI) after infusion in mPFC, whereas LMA was increased (after infusion in IL only). Therefore, our results point to the importance of cholinergic modulation in mPFC for trace conditioning and show that the observed effects cannot be attributed to reduced activity.SIGNIFICANCE STATEMENT Events are very often separated in time, in which case working memory is necessary to condition their association in “trace conditioning.” The present study used conditioning variants motivated aversively with foot shock and appetitively with food. The drug scopolamine was used to block muscarinic acetylcholine receptors involved in working memory. The results show that reduced cholinergic transmission in medial prefrontal cortex (mPFC) impaired appetitive trace conditioning at a 2 s trace interval. However, scopolamine was without effect in the aversive procedure, revealing the importance of procedural differences to the demonstration of the drug effect. The finding that blockade of muscarinic receptors in mPFC impaired trace conditioning shows that these receptors are critical modulators of short-term working memory.

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: at ground level or at a height of 70cm 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 significantly better when stimuli were presented at ground level with respect to number of trials taken to reach the criterion, percentage of correct first choices and repeated errors made. 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.

Previous in vivo electrophysiological studies suggest that the anterior cingulate cortex (ACgx) is an important substrate of novel object recognition (NOR) memory. However, intervention studies are needed to confirm this conclusion and permanent lesion studies cannot distinguish effects on encoding and retrieval. The interval between encoding and retrieval tests may also be a critical determinant of the role of the ACgx. The current series of experiments used micro-infusion of the GABAA receptor agonist, muscimol, into ACgx to reversibly inactivate the area and distinguish its role in encoding and retrieval. ACgx infusions of muscimol, before encoding did not alter NOR assessed after a delay of 20 min or 24 h. However, when infused into the ACgx before retrieval muscimol impaired NOR assessed after a delay of 24 h, but not after a 20-min retention test. Together these findings suggest that the ACgx plays a time-dependent role in the retrieval, but not the encoding, of NOR memory, neuronal activation being required for the retrieval of remote (24 h old), but not recent (20 min old) visual memory.

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.