Po. Mora et al., ROLE OF 5-HT2A AND 5-HT2A RECEPTOR SUBTYPES IN THE 2 TYPES OF FEAR GENERATED BY THE ELEVATED T-MAZE, Pharmacology, biochemistry and behavior, 58(4), 1997, pp. 1051-1057
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.