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Stress and cocaine interact to modulate Arc/Arg3.1 expression in rat brain

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Abstract

Rationale

The interaction between stress and drugs of abuse is a critical component of drug addiction, but the underlying molecular mechanisms remain elusive. Arc/Arg3.1 is an effector immediate early gene that may represent a bridge connecting short- and long-term neuronal modifications associated with exposure to stress and drugs of abuse.

Objectives

This research aims to study the modulation of Arc/Arg3.1 expression as a marker of neuronal changes associated with exposure to stress and cocaine.

Materials and methods

Rats exposed to either single or repeated stress sessions were subjected to a single intraperitoneal injection of cocaine hydrochloride (10 mg/kg) and sacrificed 2 h later. RNase protection assay was used to determine changes in Arc/Arg3.1 gene expression in different brain regions.

Results

We found significant stress–cocaine interactions in the prefrontal cortex (p < 0.001) and hypothalamus (p < 0.05). In the prefrontal cortex, acute stress potentiated cocaine-induced Arc/Arg3.1 mRNA elevation, whereas prolonged stress attenuated the response to cocaine. In the hypothalamus, although markedly reduced by acute stress, Arc/Arg3.1 gene expression was still increased by cocaine. No interaction was observed following repeated stress. Notably, cocaine-induced Arc/Arg3.1 mRNA levels were not influenced by stress in striatum and hippocampus.

Conclusions

In our experimental model, stress interacted with cocaine to alter Arc/Arg3.1 expression in a regionally selective fashion and in a way that depended on whether stress was acute or repeated. These results point to Arc/Arg3.1 as a potential molecular target modulated by stress to alter cellular sensitivity to cocaine.

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Acknowledgment

This work was supported by Ministero del Lavoro, della Salute e delle Politiche Sociali (Prot. DGRST.8/I.9.a.c./2009/P), grant to FF, and in part by Compagnia di San Paolo (3940IT/PF, pratica 2008.2177), grant to FF.

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Correspondence to Fabio Fumagalli.

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Caffino, L., Racagni, G. & Fumagalli, F. Stress and cocaine interact to modulate Arc/Arg3.1 expression in rat brain. Psychopharmacology 218, 241–248 (2011). https://doi.org/10.1007/s00213-011-2331-3

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  • DOI: https://doi.org/10.1007/s00213-011-2331-3

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