THE DORSAL RAPHE NUCLEUS IS A SITE OF ACTION MEDIATING THE BEHAVIORAL-EFFECTS OF THE BENZODIAZEPINE RECEPTOR INVERSE AGONIST DMCM

Systemic administration of benzodiazepine receptor inverse agonists le ads to behavioral changes similar to those produced by inescapable sho ck (IS). The dorsal raphe nucleus (DRN) is a critical structure mediat ing IS effects. The present experiments determined whether the DRN is a site mediating the behavioral changes produced by benzodiazepine rec eptor inverse agonists. Microinjection of the inverse agonist Methyl 6 ,7-Dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in the region of the DRN produced enhancement of fear conditioning as assessed by t he amount of freezing in the presence of shock cues as well as interfe rence with shuttlebox escape learning assessed 24 hr later. Furthermor e, lesion of the DRN blocked the effects of systemic DMCM on fear cond itioning and escape learning. These data suggest that the DRN is indee d critical in mediating these behavioral consequences of DMCM and furt her support a role for the DRN in producing the behavioral changes ind uced by IS.