Short- and long-term behavioral analysis of social interaction, ultrasonic vocalizations and social motivation in a chronic phencyclidine model.

Phencyclidine (PCP) has been suggested to induce symptoms of schizophrenia. However, animal models using PCP administration have produced ambiguous results thus far. It seems that acute effects are similar to symptoms of schizophrenia, however, it is not clear if PCP can induce permanent behavioral changes that reflect schizophrenic-like symptoms. Therefore, we assessed the ability of chronic PCP administration (3mg/kg, 14 days) to induce short or long lasting behavioral changes in rats. Social behavior, including ultrasonic vocalizations and motivation for social contact were investigated at different time points, up to 29-36 days, after cessation of PCP treatment. During a social separation test, performed at 5 and 36 days, PCP treated rats spent less time near the divider that separates them from their familiar cage mate compared with saline (SAL) treated rats. Further, at short term, PCP was able to induce a decrease in social behavior. In contrast, at long-term, PCP treated animals spent more time in contact when exposed to an unfamiliar partner as compared to SAL treated rats. But, this difference was not observed when exposed to a familiar partner. We did not find any difference in ultrasonic vocalizations at all time points. The results of our study indicate that PCP is unable to induce overt long term deficits in social interaction behavior. Rather, it seems that PCP diminishes motivation for social contact. The long-term consequences of chronic PCP administration on social behavior in rodent models remain complex, and future studies addressing this are still needed.

Novel approach to automatically classify rat social behavior using a video tracking system.

BACKGROUND: In the past, studies in behavioral neuroscience and drug development have relied on simple and quick readout parameters of animal behavior to assess treatment efficacy or to understand underlying brain mechanisms. The predominant use of classical behavioral tests has been repeatedly criticized during the last decades because of their poor reproducibility, poor translational value and the limited explanatory power in functional terms. NEW METHOD: We present a new method to monitor social behavior of rats using automated video tracking. The velocity of moving and the distance between two rats were plotted in frequency distributions. In addition, behavior was manually annotated and related to the automatically obtained parameters for a validated interpretation. RESULTS: Inter-individual distance in combination with velocity of movement provided specific behavioral classes, such as moving with high velocity when "in contact" or "in proximity". Human observations showed that these classes coincide with following (chasing) behavior. In addition, when animals are "in contact", but at low velocity, behaviors such as allogrooming and social investigation were observed. Also, low dose treatment with morphine and short isolation increased the time animals spent in contact or in proximity at high velocity. COMPARISON WITH EXISTING METHODS: Current methods that involve the investigation of social rat behavior are mostly limited to short and relatively simple manual observations. CONCLUSION: A new and automated method for analyzing social behavior in a social interaction test is presented here and shows to be sensitive to drug treatment and housing conditions known to influence social behavior in rats.

Ethological concepts enhance the translational value of animal models.

The translational value of animal models is an issue of ongoing discussion. We argue that 'Refinement' of animal experiments is needed and this can be achieved by exploiting an ethological approach when setting up and conducting experiments. Ethology aims to assess the functional meaning of behavioral changes, due to experimental manipulation or treatment, in animal models. Although the use of ethological concepts is particularly important for studies involving the measurement of animal behavior (as is the case for most studies on neuro-psychiatric conditions), it will also substantially benefit other disciplines, such as those investigating the immune system or inflammatory response. Using an ethological approach also involves using more optimal testing conditions are employed that have a biological relevance to the animal. Moreover, using a more biological relevant analysis of the data will help to clarify the functional meaning of the modeled readout (e.g. whether it is psychopathological or adaptive in nature). We advocate for instance that more behavioral studies should use animals in group-housed conditions, including the recording of their ultrasonic vocalizations, because (1) social behavior is an essential feature of animal models for human 'social' psychopathologies, such as autism and schizophrenia, and (2) social conditions are indispensable conditions for appropriate behavioral studies in social species, such as the rat. Only when taking these elements into account, the validity of animal experiments and, thus, the translation value of animal models can be enhanced.

Reproducibility and relevance of future behavioral sciences should benefit from a cross fertilization of past recommendations and today's technology: "Back to the future".

Thanks to the discovery of novel technologies and sophisticated analysis tools we can now 'see' molecules, genes and even patterns of gene expression, which have resulted in major advances in many areas of biology. Recently, similar technologies have been developed for behavioral studies. However, the wide implementation of such technological progress in behavioral research remains behind, as if there are inhibiting factors for accepting and adopting available innovations. The methods of the majority of studies measuring and interpreting behavior of laboratory animals seem to have frozen in time somewhere in the last century. As an example of the so-called classical tests, we will present the history and shortcomings of one of the most frequently used tests, the open field. Similar objections and critical remarks, however, can be made with regard to the elevated plus maze, light-dark box, various other mazes, object recognition tests, etc. Possible solutions and recommendations on how progress in behavioral neuroscience can be achieved and accelerated will be discussed in the second part of this review.

Predictions of recall and study strategy decisions after diffuse brain injury.

OBJECTIVE: To investigate relationships between self-monitoring operationalized by predicting recall and study strategy decisions made by adults with diffuse, acquired brain injury (ABI) and adults without ABI. RESEARCH DESIGN AND METHODS: Eighteen adults with ABI and 16 without ABI studied two lists of unrelated noun-pairs, made item-by-item immediate and delayed recall predictions and selected items (after predictions) to restudy again. The computer selected items for restudy based on the lowest prediction rating (i.e. unlikely to recall). A mixed list design was used to balance item selection (self or computer,within-lists) by type of prediction (immediate or delayed, between-lists). Recall was tested prior to and after restudying. HYPOTHESES: Delayed recall predictions would be more accurate than immediate recall predictions; participants would select items for restudy that corresponded with 'lower' delayed predictions (i.e. less likely to recall) and 'higher' immediate predictions (i.e. more likely to recall); for adults with ABI, recall would improve the most from restudying items selected after delayed predictions; and that recall predictive accuracy and study selection decisions are independent processes. RESULTS: Delayed recall predictions were more accurate than immediate recall predictions, though adults with ABI tended to be less accurate than controls. Both groups selected items for restudy that had relatively low prediction ratings irrespective of prediction timing. Of adults with ABI, those with low recall prior to restudy selected items that had 'high' immediate predictions (i.e. likely to recall). However, there was no greater benefit to recall using this strategy. For adults with ABI, recall improved the most from restudying items that were self-selected after delayed predictions, whereas controls' recall improved, irrespective of prediction and selection timing. Between-person correlations revealed no relationship between recall predictive accuracy and study selection strategies. CONCLUSIONS: These findings imply that adults with ABI should base strategy decisions on delayed predictions rather than on 'in the moment' immediate ones, selecting items that they have predicted will be difficult to recall. Continued efforts to disambiguate self-monitoring from strategy decisions are required before direct clinical applications can be made.