Reinforcing and discriminative-stimulus effects of two pyrrolidine-containing synthetic cathinone derivatives in rats

The molecular and behavioral aspects of alpha-pyrrolidinopentiophenone (alpha-PVP) have been characterized; however, how the structural modification of alpha-PVP affects its abuse potential is still unknown. In this study, we investigated the abuse potential of two pyrrolidinylated second-generation cathinones:4-chloro-alpha-pyrrolidinopentiophenone (4cl-alpha-PVP) and 4-chloro-alpha-pyrrolidinopropiophenone (4cl-alpha-PPP). Male Sprague-Dawley rats were trained to self-administer methamphetamine (METH, 0.05 mg.kg(-1).infusion(-1)), alpha-PVP (0.05 mg.kg(-1).infusion(-1)), 4cl-alpha-PVP (0.05 mg.kg(-1).infusion(-1)), and 4cl-alpha-PPP (0.5 mg.kg(-1).infusion(-1)) under a fixed ratio (FR)(-1) reinforcement schedule for-10 sessions. The discriminative-stimulus effect of METH (0.8 mg/kg) from saline was tested under an FR10 schedule of food delivery. alpha-PVP, 4cl-alpha-PVP and 4cl-alpha-PPP produced reinforcement behaviors and presented an inverted U-shaped dose effect. The reinforcing potency was displayed with a rank order of alpha-PVP (0.029 mg.kg(-1).infusion(-1)) > METH (0.040 mg.kg(-1).infusion(-1)) > 4cl-alpha-PVP (0.094 mg.kg(-1).infusion(-1)) > 4cl-alpha-PPP (0.51 mg.kg(-1).infusion(-1)). All three drugs were fully substituted for the discriminative-stimulus effects of METH in rats. The substitution potency for discriminative-stimulus effects of alpha-PVP (ED50 = 0.4 mg/kg) was approximately equal to that of METH (ED50 = 0.3 mg/kg), while the discriminative potency of 4cl-alpha-PVP (ED50 =-1.0 mg/kg) and 4cl-alpha-PPP (ED50 = 5 mg/kg) was approximately 3 and-16-fold less than that of METH. The rank order of potency was alpha-PVP approximate to METH > 4cl-alpha-PVP > 4cl-alpha-PPP. The present data demonstrated that 4cl-alpha-PVP and 4cl-alpha-PPP produced reinforcing effects and fully and dose-dependently substituted for the subjective effects of METH, suggesting that both 4cl-alpha-PVP and 4cl-alpha-PPP have abuse potential that may be similar to METH.

Automated summary

The study investigated the abuse potential of two pyrrolidinylated second-generation cathinones: 4-chloro-alpha-pyrrolidinopentiophenone (4cl-alpha-PVP) and 4-chloro-alpha-pyrrolidinopropiophenone (4cl-alpha-PPP). Both substances produced reinforcing effects and fully substituted for the subjective effects of METH, suggesting similar abuse potential to METH.