This study is utilizing prolonged, low level carbon monoxide (CO) exposure to produce limited brain damage which has previously been shown to produce hyperactivity in adult and 5-day-old rats. The difference in the two developmental stages is that the exposed infants recover from the hyperactivity while the adults do not. Through this model we hope to achieve the following broad objectives: 1) The first is to define neurochemical alterations, produced by CO exposure, which correlate with the development of hyperactivity at both ages. 2) The second is to define very carefully the behavioral and chemical events associated with the recovery of the young animals as they mature. 3) The third is to study the behavioral and chemical response of both types of hyperactive animal to amphetamine which is known to be therapeutic in minimal brain dysfunction accompanied by "hyperactivity" in children. Out findings to date can be summarized in two statements. 1) Our data show that there is a dose-effect relationship for the duration of CO exposure and the modification of motor behavior and that the relationship is related to age, sex and body weight. 2) The data clearly indicate that periods of CO exposure, in excess of 60 min, produce behavioral alterations and changes in brain norepinephrine, dopamine and 5-hydroxytryptamine which persist for long periods of time. The finding of a dose/duration relationship to the behavioral effect is an exceptionally important observation both in terms of understanding hypoxia and in the practical sense of establishing homogenous population for study. In this coming year we will concentrate our efforts on defining the neurochemical changes in the juvenile group (exposed at 5 days) and upon determining their response to amphetamine both as individuals and in groups.