Active heroin administration induces specific genomic responses in the nucleus accumbens shell

Abstract

Long-term drug-induced alterations in gene expression underlying neuroplasticity in the nucleus accumbens (NAc) may play a crucial role in relapse behavior in abstinent drug addicts. In this respect, stimulus-induced relapse behavior is considered as the retrieval of stored drug-related information. Because the NAc shell may determine the impact of external and internal stimuli on goal-directed behavior, we compared long-term gene expression in this brain region after active and passive administration of different drugs of abuse. We made use of a preselected set of transcripts that were down-regulated 3 wk after active i.v. heroin self-administration. We found that most of these transcripts were not down-regulated long after passive exposure to the opiate. Most of the active heroin administration-regulated transcripts were also down-regulated in the NAc shell following active cocaine administration (common denominators). As observed with passive administration of heroin, passive exposure to cocaine was found to be relatively ineffective in reducing the expression of these transcripts. This work reveals that active drug consumption during self-administration (instrumental learning) is a crucial psychological factor directing long-term genomic responses in the brain.

Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats

“…Here, we demonstrated that MPEP treatment in the NAc shell attenuated the heroin seeking behavior induced by context, which indicates the activation of mGluR5 in the NAc shell may be involved in context induced heroin seeking. With respect to opiate drugs, heroin administration leads to long-term alterations in gene expression in the NAc shell [31] . The mPFC is a brain area that has a pivotal role in relapse to opiate seeking during periods of drug absti- Figure 5.…”

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

“…Substantial evidence demonstrates that volitional (actively intended) drug intake produces distinct physiological, biochemical, and behavioral effects when compared with forced drug administration. For example, the response contingency of drug exposure robustly influences gene expression (Jacobs et al, 2002(Jacobs et al, , 2003(Jacobs et al, , 2005, neural activation (Chang et al, 1994;Peoples and West, 1996;Stuber et al, 2005), and resultant extracellular neurochemistry (Di Ciano et al, 1996;Hemby et al, 1997;Jacobs et al, 2003;Lecca et al, 2007;Orejarena et al, 2009;You et al, 2007). With specific regard to nicotine, differential effects of volitional SA vs forced drug administration have been observed on a 4 b 2 nAChR expression (Metaxas et al, 2010), cortical glutamatergic projection activity and plasticity mechanisms in the ventral tegmental area (VTA) (McFarland et al, 2003;You et al, 2007), and plasma corticosterone levels (Donny et al, 2000).…”

Extracellular Matrix Plasticity and GABAergic Inhibition of Prefrontal Cortex Pyramidal Cells Facilitates Relapse to Heroin Seeking

“…With respect to opiate drugs, heroin administration leads to long-term alterations in gene expression in the NAc shell (Jacobs et al, 2002). At the cellular level, changes in neuronal connectivity and neuronal physiology have been observed after opiate exposure.…”