Acute effects of clomipramine and fluoxetine on dorsal periaqueductal grey-evoked unconditioned defensive behaviours of the rat.
BACKGROUND
Several antidepressants attenuate conditioned escape behaviours reinforced by the terminus of an electrical stimulus applied to the dorsal periaqueductal grey (DPAG).


OBJECTIVE
The present study examined whether the antidepressant and antipanic drugs clomipramine (CLM) and fluoxetine (FLX) also attenuate the DPAG-evoked unconditioned defensive behaviours.


METHODS
Rats with electrodes in the DPAG were electrically stimulated in the absence of any treatment or 30 min after injections of CLM, FLX or saline. Threshold functions of cumulative response frequencies were fitted through the logistic model and compared using likelihood ratio coincidence tests.


RESULTS
CLM produced non-linear effects on galloping, for which median thresholds (I50) were significantly increased (19 +/- 2%) or decreased (22+/-2%) with 5 mg/kg and 10 mg/kg, respectively, or did not change with 20 mg/kg. The latter dose further increased the I(50) of micturition (38 +/- 1%) and decreased the defecation output (-33 +/- 15%). FLX significantly increased the I50 of immobility (22 +/- 2%) and galloping (25 +/- 3%) with 1 mg/kg and 5 mg/kg, respectively. Moreover, corresponding doses either decreased the maximum output (-25 +/- 13%) or increased the I50 (56 +/- 11%) of defecation. Saline was ineffective.


CONCLUSIONS
While the attenuation of defecation and micturition by 20 mg/kg CLM suggests a peripheral antimuscarinic action, CLM non-linear effects on galloping were most likely due to its differential action on monoaminergic and cholinergic central mechanisms. In contrast, the attenuation of immobility, galloping and defecation by low doses of FLX suggests a serotonin-mediated antiaversive action. Finally, CLM and FLX acute effects on DPAG-evoked unconditioned galloping response were strikingly similar to those reported for DPAG-evoked shuttle-box conditioned escape.
Schenberg
Luiz Carlos
LC
Departamento de Ciências Fisiológicas - Centro Biomédico, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468 (Maruípe), 29040-090 Vitória-ES, Brazil. schenber@terra.com.br
Capucho
Larissa Bustamante
LB
Vatanabe
Richardo Ossamu
RO
Vargas
Leila César
LC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002997:Clomipramine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003674:Defense Mechanisms; D004558:Electric Stimulation; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D002997:Clomipramine; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors