These predisposing

factors, either innate or acquired, determine individual “affective styles”2,34 or coping strategies,26 which are thought to play an important role in vulnerability to psychopathology. Animal models Some of the neurobiological mechanisms underlying anxiety may already be present in very simple organisms, such as the snail Aplysia, which can show forms of learning akin to anticipatory and chronic anxiety.35 However, most animal models of anxiety are based on the use of mammalian species, particularly rats and mice.36-42 These models fall into two broad categories. In the first one, animals are confronted Inhibitors,research,lifescience,medical with situations that generate an anxious state (state anxiety models). This state of anxiety can be either conditioned (eg, conditioned fear, avoidance, and punishment-induced conflict tests) or unconditioned (eg, aversive and ethological conflict tests). Inhibitors,research,lifescience,medical In the second category, the models are concerned with

trait or “pathological” anxiety: genetic manipulations (transgenic or “knockout” animals) or selective breeding creates lines of rats or mice that permanently express an increased or decreased level of anxiety. Functional neuroanatomy As already suspected by Letourneau Inhibitors,research,lifescience,medical and others, emotional. experience and the associated behavioral responses are likely to activate specific circuits in the brain. The search for the neuroanatomical

substrates of fear and anxiety has been a successful field of research over the last decades. For a long time, it was assumed that emotions, including fear and anxiety, were almost exclusively generated or processed in a “primitive” part of the brain, ie, the limbic Inhibitors,research,lifescience,medical system (“the emotional brain”). The view that emotions and cognitions are separate functions of the brain and must therefore have different underlying neuroanatomical substrates is probably responsible for this simplification. As pointed out by LeDoux Inhibitors,research,lifescience,medical in a recent review,43 modern research with the most advanced neuro-imaging technologies still uses this dichotomic approach to higher brain functions as a post hoc explanation: “When a so-called emotional task is used, and a limbic area is activated, the activation is explained by reference to the fact that limbic areas mediate emotions. And when a limbic area is Entinostat full report activated in a cognitive task, it is often assumed that there must have been some emotional undertone to the task.” However, neuroanatomical and behavioral data obtained during the last decades clearly indicate that this dichotomy between cognitive and emotional processes is obsolete. The locus ceruleus and arousal Autonomic activation and increased arousal are among the earlier psychophysiological responses observed in a state of fear or anxiety.