Individual differences in cocaine seeking during voluntary abstinence predicts cocaine relapse and the circuitry mediating relapse.

Abstract

There are no FDA-approved treatments to facilitate recovery from cocaine use disorder. Contingency management offers non-drug reinforcers to encourage abstinence and is effective at reducing drug seeking during treatment, but once discontinued, relapse rates increase. We sought to establish a choice-based rodent model of voluntary abstinence (VA) from cocaine to test the ability of ceftriaxone, an antibiotic consistently shown to prevent relapse to cocaine seeking in rodents, to attenuate relapse after discontinuation of VA, and to investigate relapse-induced neuronal activation via c-Fos expression. Male Sprague-Dawley rats self-administered sucrose pellets for 5days and intravenous cocaine for 12days. Rats then underwent 14days of voluntary or forced abstinence. VA sessions entailed the opportunity to choose between sucrose and cocaine delivery in discrete trials (20 trials/day). Ceftriaxone (or vehicle) was administered during the last 7days of abstinence. During a relapse test, only the cocaine-paired lever was available and presses on the lever delivered cocaine-paired cues. There were more presses on the sucrose lever during VA, but cocaine intake did not decline to zero. Ceftriaxone had no effect on cocaine intake during VA. Neither ceftriaxone nor VA reduced cocaine seeking during the relapse test, and cocaine intake during VA positively correlated with cocaine seeking during the test in vehicle-treated animals. Relapse-induced c-Fos expression was found to be greater in the ventral orbitofrontal cortex following VA. Sucrose availability leads to a decrease in, but not cessation of, cocaine seeking and a differential engagement of the circuitry underlying relapse.