Behavioral and biochemical studies of the substrates of median raphe lesion induced hyperactivity

Many authors have demonstrated that electrolytic lesions of the median raphe nucleus lead to dramatic hyperactivity, but little is known as to the neural substrates of this effect. In the current series of experiments we investigated this question by examining locomotor activity and forebrain serotonin levels after the placement of wire knife cuts in various locations around the median raphe. Activity was measured in a five minute open field test and a one hour tilt cage test. Knife cuts designed to transect the major ascending serotonergic projections of the median raphe led to a pronounced depletion of forebrain serotonin, but had no effect on locomotor activity in either testing situation. Knife cuts located antero-ventral to the median raphe, designed to interrupt raphe connections with the ventral tegmental area and interpeduncular nucleus, increased activity in the tilt cage but not in the open field test. These cuts produced only small effects on forebrain serotonin levels. Knife cuts caudal to the median raphe failed to influence forebrain serotonin levels, but produced a significant increase in both open field and tilt cage activity. The effects of the posterior and the anteroventral cuts on tilt cage locomotion were additive, suggesting that different fiber systems were damaged by the two cuts. These results demonstrate that it is possible to double dissociate changes in forebrain serotonin levels and locomotor activity with lesions in the vicinity of the median raphe and further show that ascending projections are unlikely to be the only pathways involved in the effects of median raphe lesions on locomotor behavior.