Distinct populations of neurons activated by heroin and cocaine in the striatum as assessed by catFISH

Despite the still prevailing notion of a shared substrate of action for all addictive drugs, there is evidence suggesting that opioid and psychostimulant drugs differ substantially in terms of their neurobiological and behavioural effects. These differences may reflect separate neural circuits engaged by the two drugs. Here we used the catFISH technique to investigate the degree of overlap between neurons engaged by heroin versus cocaine in adult male Sprague-Dawley rats. The catFISH technique is a within-subject procedure that takes advantage of the different transcriptional time-course of the immediate-early genes homer 1a and arc to determine to what extent two stimuli separated by an interval of 25 min engage the same neuronal population. We found that throughout the striatal complex the neuronal populations activated by non-contingent intravenous injections of cocaine (800 µg/kg) and heroin (100 and 200 µg/kg), administered at an interval of 25 min from each other, overlapped to a much lesser extent than in the case of two injections of cocaine (800 µg/kg), also 25 min apart. The greatest reduction in overlap between populations activated by cocaine and heroin was in the dorsomedial and dorsolateral striatum (~30% and ~22%, respectively, of the overlap observed for the sequence cocaine-cocaine). Our results point toward a significant separation between neuronal populations activated by heroin and cocaine in the striatal complex. We propose that our findings are a proof of concept that these two drugs are encoded differently in a brain area believed to be a common neurobiological substrate to drug abuse.