Neuropharmacology of the afferent projections from the lateral habenula and substantia nigra to the anterior raphe in the rat

Abstract

Previous neuroanatomical studies have demonstrated the existence of major afferent projections to the nucleus raphe dorsalis originating in the lateral habenula and substantia nigra. These projections have a predominantly suppressive effect on raphe unit activity. The present acute electrophysiological study in anesthetized rats evaluated: (a) the effects of pharmacological blockade of GABAergic transmission on the suppression of activity of units in the nuclei raphe dorsalis and raphe medianus by stimulation of the lateral habenula, and (b) the effects of pharmacological blockade of GABA, dopamine, acetylcholine, glycine, opiates, serotonin, norepinephrine and histamine on the suppression of raphe activity by electrical stimulation of the substantia nigra. Results showed that the GABA bloeker, picrotoxin, attenuated the effects of lateral habenula stimulation on unit activity in the raphe dorsalis and medianus and that GABA may exert a tonic inhibitory influence on spontaneous unit activity in the raphe. The effects of stimulation in the nigra on raphe dorsalis and medianus neuronal activity were not blocked by any of the 10 drugs tested. Indirect evidence was obtained, however, that norepinephrine and possibly histamine exerted an excitatory effect on raphe units since drugs which block these transmitters tended to enhance the suppressive effects of nigral stimulation. The present results do not permit identification of the neurotransmitter which mediates the marked suppression of unit activity in the anterior raphe produced by electrical stimulation of the substantia nigra.