Distinct Populations of Neurons Activated by Heroin and Cocaine in the Striatum as Assessed by catFISH

Abstract

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 behavioral effects. These differences may reflect separate neural circuits engaged by the two drugs. Here we used the catFISH (cellular compartment analysis of temporal activity by fluorescence in situ hybridization) 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 noncontingent intravenous injections of cocaine (800 g/kg) and heroin (100 and 200 g/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 g/kg), also 25 min apart. The greatest reduction in overlap between populations activated by cocaine and heroin was in the dorsomedial and dorsolateral striatum (ϳ30% and ϳ22%, 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.

Facilitating mGluR4 activity reverses the long-term deleterious consequences of chronic morphine exposure

“…The present study is the first report that facilitating glutamate mGluR4 activity can relieve the deleterious long-term behavioral and molecular consequences of opiate, but not cocaine, abuse. These results highlight the neurobiological differences between opiate and psychostimulant abstinence, arguing against a unitary view of drug addiction (9,41). They also substantiate the view of negative affect in opiate abstinence as resulting from excessive activity of striatal D2-MSNs, more specifically in the NAc (33)(34)(35)58).…”

“…Thus, prolonged abstinence from morphine, and not cocaine, inhibited the expression of a set of genes in D1-and D2-MSNs. These data substantiate the notion of differential neurobiological substrates involved in opiate versus psychostimulant addiction (9,14,41,42).…”

Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses

“…The following day (day 1), the mouse was injected with saline and, on day 2, with cocaine. The calcium signal was recorded for 10 min, beginning 10 min after injection, assuming that changes in GCaMP activity would correlate with the quick rise of ARC mRNA expression ( Vassilev et al, 2020 ; Guzowski et al, 2005 ). After imaging, the mouse was perfused to preserve ARC expression related to the neural activity (25–30 min after cocaine injection; Figure 6A ).…”

Effect of pharmacological manipulations on Arc function

“…In a recent study, activation of neural activity patterns in the striatum was measured using cellular compartment analysis of temporal activity by fluorescence in-situ hybridization (catFISH) for Arc and Homer1a . Although separate injections of cocaine and heroin induce Arc and Homer1a with a similar time course, injection of cocaine followed by heroin 25 ​min later engages distinct patterns of neurons in the striatum, providing supporting evidence that these two drugs operate through different mechanisms in the brain and encode distinct representations in the striatum ( Vassilev et al., 2020 ).…”