Acute effects of clomipramine and fluoxetine on dorsal periaqueductal grey-evoked unconditioned defensive behaviours of the rat

Abstract

Rationale: 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 I₅₀ 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.