ROLE OF 5-HT2A AND 5-HT2A RECEPTOR SUBTYPES IN THE 2 TYPES OF FEAR GENERATED BY THE ELEVATED T-MAZE

To study the role of 5-HT2A and 5-HT2C receptor subtypes in anxiety, t he behavioral effects of drugs that either block or stimulate these re ceptors were measured in an animal model of anxiety, the elevated T-ma ze. One arm of the maze is enclosed by walls and stands perpendicular to the two open arms. Inhibitory (passive) avoidance-representing lear ned fear-was measured by placing a rat at the end of the enclosed arm and recording the time to leave this arm with the four paws during thr ee consecutive trials. After 30 s, the same animal was placed at the e nd of one of the open arms and the time to leave this arm with the fou r paws was recorded. This one-way escape response represents unconditi oned fear. The TP injection of the preferential 5-HT2C receptor agonis ts mCPP and TFMPP (0.1-0.8 mg/kg), 25 min before the experimental sess ion enhanced inhibitory avoidance. In contrast, the same drugs either tended to impair (mCPP) or significantly inhibited (TFMPP) one-way esc ape. The preferential 5-HT2A agonist DOI (0.03-0.3 mg/kg) did not chan ge either inhibitory avoidance or one way escape. Inhibitory avoidance was impaired by the selective 5-HT2C antagonists SB 200646A (3.0-30 m g/kg) and SDZ SER 082 (0.1-1.0 mg/kg), by the 5-HT2A antagonist SR 463 49B (1.0-10.0 mg/kg), and by the mixed 5-HT2A/2C antagonist ritanserin (0.3-3.0 mg/kg). However, it was not affected by the selective 5-HT2A antagonist RP 62203 (0.25-4.0 mg/kg). All the 5-HT2 antagonists used were ineffective on one-way escape. Therefore, conditioned fear seems to be tonically facilitated through 5-HT2C receptor stimulation, altho ugh the 5-HT,, receptor may also participate in its regulation. Uncond itioned fear might be phasically inhibited by 5-HT2C receptor activati on. (C) 1997 Elsevier Science Inc.