The Maudsley rat strains may be one of the best-kept secrets in Biological Psychiatry. Selectively bred by Broadhurst in the 1950s and 1960s for their high and low levels of emotionality (Open Field Defecation; OFD), the Maudsley Reactive and Non-Reactive rats represent a genetically-based """"""""animal model"""""""" for the study of anxiety disorders. Surprisingly, reports on the behavioral pharmacology of these Maudsley rats do not exist. This is perhaps because of two problems associated with OFD testing: (1) it does not lend itself to repeated measures designs and (2) """"""""floor effects"""""""" (i.e., zero defecation in the Non-Reactive rats), which make drug manipulations difficult to interpret. Using two of the three strains of Maudsley rats which Dr. Gordon Harrington at the University of North Iowa has been breeding, we have shown that Non-Reactive (MNRA/Har) rats differ from Reactive (MR/Har) rats in their basal performance in the Conditional Suppression of Drinking (CSD) paradigm, with the MNRA/Har rats accepting more shocks than MR/Har rats. This CSD procedure, related to the Vogel and Geller-Seifter procedures, has been used extensively in the study of """"""""anxiety"""""""" and anti-anxiety agents. The first objective of the present studies is to determine the basal CSD performance of Harrington's second Non-Reactive strain (MNR/Har). These results will shed light on the relationship between OFD and CSD behavior. Finally, because the CSD procedure is a non-zero baseline procedure employing repeated measures, a series of behavioral pharmacology studies will be conducted. Specifically, the effects of benzodiazepine agonists, the benzodiazepine antagonist Ro15-1788, benzodiazepine """"""""inverse agonists"""""""" (FG-7142 and CGS-8216), and barbiturates will be determined in these three Maudsley rat strains. Based on the greater number of benzodiazepine receptors in the Non-Reactive rats compared to the Reactive rats, the Non-Reactive rats should show a greater response to both the benzodiazepine agonists and inverse agonists. Preliminary data with a single dose of diazepam (5 mg/kg) suggest that this may be the case. The barbiturates represent """"""""controls"""""""", with no strain differences expected to occur. The results of these studies will greatly enhance our understanding of the behavior and pharmacology of these Maudsley rat strains, and will open up areas for additional basic and clinical investigations into the nature of anxiety disorders and emotional behavior.
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