Evidence against serotonin involvement in the hyperactivity produced by injections of muscimol into the median raphe nucleus.

Microinjections of muscimol into the median raphe nucleus were found to result in pronounced hyperactivity which could not be attenuated by the serotonin depletion produced either by systemic treatment with p-chlorophenylalanine or by intra-raphe injections of 5,7-dihydroxytryptamine. Furthermore, hyperactivity could not be produced by intra-median raphe injections of serotonin or of fenfluramine, compounds which would be expected to inhibit serotonergic raphe cells. These results argue strongly against an essential involvement of serotonin in mediating the effects of intra-median raphe muscimol injections. Muscimol failed to produce hyperactivity, however, when injected into rats who had previously received an electrolytic median raphe lesion. This finding suggests that muscimol injected into the median raphe produces hyperactivity as a result of an action on local cell bodies, rather than by diffusion to a distant site. The simplest explanation of the current results is that muscimol injected into the median raphe produces hyperactivity as a result of an inhibition of nonserotonergic cells within the median raphe nucleus.