Effects of chronic amphetamine treatment on cocaine‐induced facilitation of intracranial self‐stimulation in rats

Abstract

Amphetamine is a monoamine releaser and candidate agonist medication for cocaine dependence. Chronic amphetamine treatment decreases cocaine self‐administration by rats, nonhuman primates and humans. This study tested the hypothesis that chronic amphetamine would decrease abuse‐related facilitation of intracranial self‐stimulation (ICSS) by cocaine in rats. Male Sprague‐Dawley rats were equipped with electrodes targeting the medial forebrain bundle and trained to respond under a fixed‐ratio 1 schedule for 0.5 sec trains of electrical stimulation. Stimulation intensity was individually determined in each rat, and frequency varied from 56–158 Hz in 0.05 log units during each session. Effects of 10 mg/kg cocaine on ICSS were determined before, during and after 14‐day continuous infusion with saline (N=5) or amphetamine (0.32 mg/kg/hr, N=5). Saline treatment had no effect on ICSS, and cocaine produced comparable facilitation of ICSS before, during and after saline treatment. Amphetamine facilitated ICSS throughout the 14‐day treatment, and termination of amphetamine decreased ICSS below pre‐treatment baseline. Cocaine facilitated ICSS before and after amphetamine, but during amphetamine treatment, it did not facilitate ICSS above levels produced by amphetamine alone. These findings suggest that chronic amphetamine decreases abuse‐related stimulus effects of cocaine. Funded by R01 DA026946