However, these data could also

be explained by a reduced ability of stressed animals to associate reinforcing stimulus with the environment where this stimulus is presented. Deficits in associative learning have been observed in animals exposed to electric shocks15 and subtle alterations of attention induced by “nonpertincnt” stimuli have also been reported.16 Self-stimulation behavior is a very useful way for studying positive reinforcements and motivational or hedonic states. The self-stimulation technique allows a rat implanted with an electrode in a particular Inhibitors,research,lifescience,medical reward area of the brain to selfadminister weak electrical pulses. Such stimulation can have very intense reinforcing properties. Thus, the greater the rewarding Inhibitors,research,lifescience,medical properties of the stimulation, the more the rat will self-stimulate. The threshold for self-stimulation behavior can thus be used as an index of its hedonic/anhedonic state.17 An increase in this threshold will indicate a decreased sensitivity to reward. By allowing stimulation of the mcsocorticolimbic structures, it, is possible to obtain very intense self-stimulation behavior because this stimulation activates directly the neuronal substrates involved in motivational processes. In our model, self-stimulation behavior induced by activation Inhibitors,research,lifescience,medical of

the ventral tegmental area was used because corticolimbic projections of this brain structure constitute the main source of the dopaminergic innervation of the brain, which plays a major role in motivational and rewarding processes.18 Effects of chronic mild stress on sensitivity to pleasure in rats By using a chronic, unpredictable, Inhibitors,research,lifescience,medical mild stress regimen as the etiological factor and variations of ventral tegmentum selfstimulation threshold as the anhedonia scale, it was shown that rats exposed for 3 weeks to such a stress regimen exhibited an increase

in self-stimulation threshold (Figure 1), ie, Inhibitors,research,lifescience,medical a decrease in their sensitivity to pleasure. This effect progressively developed over the first, 2 weeks of stress, lasted until the end of the stress period, and gradually disappeared thereafter. Nonstressed animals did not develop such an anhedonic state. This increase in self-stimulation threshold is Ketanserin compatible with a decrease in the reinforcing efficacy of the stimulation, reflecting the gradual development of an anhedonic state induced by stress. The decreased sensitivity to reinforcing stimuli as well as the progressive development of stress effects resemble certain aspects of depression in man. These observations Protein Tyrosine Kinase inhibitor already provide this animal model of depression with a certain degree of theoretical validity. Figure 1. Anhedonia induced by a chronic mild stress regimen in rats. Variations in self-stimulation threshold in stressed (blue squares) and nonstressed (open circles) animals are shown as a function of stress exposure time (shaded area). Asterisks indicate statistically …