Long-term effects of clomipramine and fluoxetine on dorsal periaqueductal grey-evoked innate defensive behaviours of the rat.
BACKGROUND
The defensive responses induced by electrical stimulation of dorsal periaqueductal grey (DPAG) of the rat have been proposed as a model of panic attacks in humans.


OBJECTIVE
The present experiments were carried out 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), fluoxetine (FLX; 1 and 5 mg/kg) or saline. Long-term effects were assessed prior to the treatment to avoid acute drug effects. Threshold logistic functions of defensive responses were compared by likelihood ratio coincidence tests.


RESULTS
CLM attenuated DPAG-evoked defensive behaviours at a time-course 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 responses disclosed selective threshold increases of galloping (75%) and trotting (138%) with 5 and 10 mg/kg, respectively. Thresholds of micturition were markedly increased (87%) by 5 mg/kg CLM. In turn, FLX (1 mg/kg) virtually abolished the galloping response. No threshold changes were observed following the long-term administration of the higher dose of either CLM or FLX. Saline-treated rats had a significant increase (35%) in galloping thresholds only.


CONCLUSIONS
The present data partially validate the DPAG-evoked defence reaction of the rat as a model of panic attacks in humans. Attenuation of galloping by lower doses of FLX and CLM also suggests the prominent modulation of this response by serotonin.
Vargas
L C
LC
Department of Physiological Sciences, Biomedical Center, Federal University of Espírito Santo, Vitória-ES, Brazil.
Schenberg
L C
LC
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology*; D003672:Defecation / Q000187:drug effects; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005473:Fluoxetine / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016584:Panic Disorder / Q000188:drug therapy / Q000523:psychology; D010487:Periaqueductal Gray / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014554:Urination / Q000187:drug effects
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D006993:Hypnotics and Sedatives; D005473:Fluoxetine; D002997:Clomipramine