LESION OF THE HABENULAR EFFERENT PATHWAY PRODUCES ANXIETY AND LOCOMOTOR HYPERACTIVITY IN RATS - A COMPARISON OF THE EFFECTS OF NEONATAL ANDADULT LESIONS

Recent studies have implicated the habenula in modulating states of ar ousal and chronic responses to stress. We examined whether lesion of t he habenula efferent pathway, the fasciculus retroflexus (FR), at eith er 3 (P3) or 70 (P70) days of age affects stress-related anxiety (elev ated plus-maze test) and activity levels (open-held test) in rats test ed as adults. Both P3- and P70-lesioned rats showed chronically elevat ed plasma levels of corticosterone. Rats receiving FR lesions as neona tes (P3) exhibited greater open arm avoidance on the elevated plus-maz e than controls 2 months postoperatively, suggesting a heightened stat e of anxiety. In contrast, P70-lesioned rats behaved similarly to cont rols on the plus-maze, but showed increased locomotion and increased g rooming in the open field, effects not observed in P3-lesioned rats. W hen an additional stressful condition was imposed (5 days of social is olation plus 24 h food deprivation) before testing, both FR-lesion gro ups showed an attenuation of the normal behavioral responses (decrease d open-arm entries/time in open arms, increased freezing). The effects of FR lesions on activity and behavioral indices of anxiety may be du e to disruption of lateral habenular projections to dopaminergic neuro ns in the ventral tegmentum and/or projections to regions containing h igh concentrations of benzodiazepine receptors, the median and dorsal raphe and dorsal periaqueductal gray. Behavioral differences observed as a function of lesion age suggest differential capabilities of P3- a nd P70-lesioned rats to utilize compensatory mechanisms to correct FR lesion-induced deficits.