| Chapter 1 will provide a brief introduction to the neurobiology of anxiety, with an emphasis on three issues that have guided the current research. First, behavioral models of anxiety that have been useful in understanding its biological bases will be described. Second, the roles of the septum, hippocampus and amygdala in anxiety will be briefly summarized. Third, the antianxiety (anxiolytic) potential of a number of novel compounds will be described, as well as their effects in animal models of anxiety and in human anxiety.;Chapter 2 describes four studies of the anxiolytic effects of the cyclic polypeptide somatostatin in two, extensively validated rat models of anxiolytic drug action: the elevated plus-maze and the shock-probe burying test. In particular, two isoforms of somatostatin (SST 14 and SST28) were microinfused into the central amygdala, the lateral septum, and the striatum (Yeung et al., 2011), with anxiolytic-like effects found in the first two structures but not the last, thus demonstrating the site-specificity of the results.;In chapter 3, I conduct a critical test of Neil McNaughton's hippocampal theta model of anxiolytic drug action. McNaughton and colleagues have repeatedly demonstrated that clinically proven anxiolytic drugs, regardless of their individual mechanisms of action, reliably suppress brain-stem evoked hippocampal theta. Such demonstrations, however, offer only weak evidence of the validity of any particular model of anxiolytic drug action, be it behavioral or neurophysiological. Phenytoin, a well-known antiepileptic drug with no known anxiolytic potential, was used to test the predictive validity of the theta suppression model.;Chapter 4 summarizes the major results of these studies and their implications for current neuropharmacology theories of anxiety. |
