Opposed regulation by dorsal raphe nucleus 5-HT pathways of two types of fear in the elevated T-maze.

To investigate the influence of dorsal raphe nucleus (DRN) 5-HT pathways on different types of fear, we microinjected into the rat DRN the benzodiazepine inverse agonist FG 7142 and the excitatory amino acid kainic a acid. In addition, we systemically administered the 5-HT releasing drug D-fenfluramine. The behavioral effects of these drugs were measured in an elevated T-maze, consisting of three arms of equal dimensions (50 x 10 cm), elevated 50 cm from the floor. One arm is enclosed by walls (40 cm) and stands perpendicular to the two open arms. Inhibitory (passive) avoidance--representing learned fear--was measured by placing a rat at the end of the enclosed arm and recording the time to withdraw from this arm with the four paws during three consecutive trials. Soon afterwards, the same animal was placed at the end of one of the open arms and the time to withdraw from this arm with the four paws was recorded. This one-way escape response represents unconditioned fear. Intra-DRN FG 7142 (40 pmol) facilitated inhibitory avoidance (anxiogenic effect), but did not affect one-way escape. Kainic acid (60 pmol) also facilitated inhibitory avoidance and, in addition, impaired one-way escape (anxiolytic effect). These effects are unlikely to be due to motor deficit, because intra-DRN kainate did not change locomotor activity and rearing behavior of rats placed inside a circular arena for 10 min. Finally, D-fenfluramine (0.03, 0.1, and 0.3 mg/kg, IP) tended to enhance inhibitory avoidance while depressing one-way escape in a dose-dependent way. Because the three drug treatments are believed to increase 5-HT release from DRN nerve terminals, these results support the hypothesis that ascending DRN 5-HT pathways facilitate learned fear while inhibiting unconditioned fear. The former may be related to generalized anxiety and the latter to panic disorder.