Lc. Vargas et Lc. Schenberg, Long-term effects of clomipramine and fluoxetine on dorsal periaqueductal grey-evoked innate defensive behaviours of the rat, PSYCHOPHAR, 155(3), 2001, pp. 260-268
Rationale: The defensive responses induced by electrical stimulation of dor
sal periaqueductal grey (DPAG) of the rat have been proposed as a model of
panic attacks in humans. Objective: The present experiments were carried ou
t to evaluate the long-term effects of clinically effective panicolytics on
these responses. Methods. Rats that had electrodes implanted into the DPAG
were treated for 21 days with clomipramine (CLM; 5, 10 and 20 mg/kg), fluo
xetine (FLX; I and 5 mg/kg) or saline. Long-term effects were assessed prio
r to the treatment to avoid acute drug effects. Threshold logistic function
s of defensive responses were compared by likelihood ratio coincidence test
s. Results: CLM attenuated DPAG-evoked defensive behaviours at a timecourse
similar to that observed in panic therapy. Administration of 10 mg/kg CLM
for 21 days produced significant increases in the thresholds of immobility
(24%), running (49%) and jumping (45%). Splitting of running into single re
sponses disclosed selective threshold increases of galloping (75%) and trot
ting (138%) with 5 and 10 mg/kg, respectively. Thresholds of micturition we
re markedly increased (87%) by 5 mg/kg CLM. In turn, FLX (1 mg/kg) virtuall
y abolished the galloping response. No threshold changes were observed foll
owing the long-term administration of the higher dose of either CLM or FLX.
Saline-treated rats had a significant increase (35%) in galloping threshol
ds only. Conclusions: The present data partially validate the DPAG-evoked d
efence reaction of the rat as a model of panic attacks in humans. Attenuati
on of galloping by lower doses of FLX and CLM also suggests the prominent m
odulation of this response by serotonin.