Assessment of Reinforcing Effects of Benztropine Analogues and Their Effects on Cocaine Self‐Administration: Comparisons with Monoamine Uptake Inhibitors

Abstract

Reinforcing effects of monoamine uptake inhibitors (cocaine, nisoxetine, citalopram, WIN 35428, methylphenidate (MPD), AHN 1055 (4′4″diF‐benztropine), AHN 2005 (N‐allyl 4′4″diF‐BZT), and JHW 007 (N‐butyl 4′4″diF‐BZT) were assessed, along with their effects on cocaine self administration. Rats self administered cocaine (.03–1 mg/kg/injection) or saline on a fixed ratio 5 response schedule. The cocaine dose effect curve was bitonic, with maximum responding maintained at 0.3 mg/kg/inj, iv, and low rates maintained by saline. WIN 35428, MPD, and AHN 1055 maintained responding above saline levels, with cocaine equipotent to MPD, 10‐fold < WIN 35428, and more effective than AHN 1055. None of the other drugs maintained responding. AHN 2005 and JHW 007 administered before sessions (10–100 mg/kg po) produced dose related decreases in cocaine self administration, shifting the dose effect curve down, without effects on responding maintained by food reinforcement. Increasing doses of AHN 1055 (10–100 mg/kg po) shifted the cocaine self administration dose effect curve up, to the left and down. MPD (3–30 mg/kg po) dose dependently shifted the cocaine self administration dose effect curve leftward, whereas both nisoxetine and citalopram produced relatively small shifts down that did not depend on dose. The effects suggest that the BZT analogues may have utility as medications for cocaine abuse. Support by NIDA IRP.