Dissociation of behavioral changes in rats resulting from lesions of the habenula versus fasciculus retroflexus and their possible anatomical substrates.

Lesions in either the habenula or its primary efferent pathway, the fasciculus retroflexus (FR), impaired avoidance responding. However, lesions of only the FR provided a persistent elevation of locomotor activity. Immunocytochemical study of the interpeduncular nucleus (IPN) through injection of retrograde tracers into the IPN and the overlying ventral tegmental area indicated that habenular lesions spared both rostral habenula and forebrain projections to the caudal midbrain, but these projections were axotomized by FR lesions. Rostral sparing of the habenula resulted in normal peptidergic staining in the IPN, and normal cholinergic innervation was absent. Performance of individual rats in behavioral tests was consistent with variations in anatomical sparing. Such considerations may account for previous discrepancies in functional effects of habenular lesions.