Does progesterone potentiate the in vitro effect of cocaine on papillary myocardium in Long-Evans rats?

Cocaine's cardiotoxicity was reported in our laboratory to be augmented by progesterone. This study was designed to replicate these findings and determine the mechanism. Rats were pretreated with progesterone (study) or vehicle (control). Papillary muscles were attached to transducers in Krebs' baths. Paced contractility parameters were measured while increasing concentrations of cocaine, norepinephrine, or tetrodotoxin were added. In nine baths, yohimbine was added before the cocaine. Twelve rats were pretreated with reserpine, and cocaine added to the baths. In muscles from nonreserpinized control rats, there was a small positive inotropic effect (8.6% above baseline) at 10(-6) M cocaine, not seen in study muscles. There were no differences between study and control muscles in cocaine concentrations at which muscles became acontractile, nor in responses to norepinephrine, tetrodotoxin, or to cocaine after the addition of yohimbine or following reserpine pretreatment. We could not replicate cocaine's previously reported increased negative inotropic effect in progesterone-treated rats, nor was there evidence supporting possible mechanisms for this reported effect.