The Influence of Hypoxia on Avoidance Learning, Intra-Cranial Self-Stimulation and Drinking Behavior

In this thesis we described the effects of hypoxia on three types of functional behavioL avoidance learning, self-stimulation and drinking behavior. Depth and induction method of hypoxia were chosen to secure maximal survival of the animals. The aim was to evaluate which behavioral paradigm could be used in pharmacological research for detection of drugs that could protect the brain against hypoxia. In the first paradigm (Chapter I) guinea-pigs were trained twice daily on five consecutive days to learn to avoid an electrical shock (unconditioned stimulus) upon presentation of an auditory stimulus (conditioned stimulus). In control animals the number of correct responses increased in the course of the training period. In addition, more correct responses were made during the second daily training session as compared to the first session. When the animals were exposed to hypoxia (1 min. 100% nitrogen) immediately after each training session acquisition was not attenuated. However, the level of performance during the second session was reduced to that seen in the first session of that same day. This effect was probably due to a blockade of either the development or retrieval of an intermediate memory trace which contained new information learned in the first session. Given both the stability and the specificity of the induced effect the paradigm seemed to be suitable for pharmacological research. Four compounds; flunarizine, nimodipine, nifedipine and verapamil were tested. Three of them were known to have anti-hypoxic effects in simple survival models. Only tlunarizine could antagonize the amnesic effects. Interestingly, it was also the only drug known to have direct effects on brain cells. In the next paradigm self-stimulation behavior was used (Chapter 3-6). Rats were trained to obtain electrical brain stimulation in the lateral hypothalamus by pressing a lever. Trained animals reached an average response rate of one hundred responses in one minute. This response rate was reduced immediately after exposure to normobaric hypoxia but it normalized within ten minutes. These effects were reduced after a second exposure to hypoxia. This form of adaptation did not continue after subsequent exposures. Self-stimulation was also significantly reduced when the sessions were held under hypobaric conditions. At a barometric pressure of 300 mm.Hg a significant reduction of the response rate was observed during the whole session. A progressive slow adaptation was seen after several sessions in the hypobaric environment.