Enhanced cortical and accumbal molecular reactivity associated with conditioned heroin, but not sucrose-seeking behaviour
Article first published online: 19 JUN 2006
Journal of Neurochemistry
Volume 98, Issue 3, pages 905–915, August 2006
How to Cite
Koya, E., Spijker, S., Voorn, P., Binnekade, R., Schmidt, E. D., Schoffelmeer, A. N. M., De Vries, T. J. and Smit, A. B. (2006), Enhanced cortical and accumbal molecular reactivity associated with conditioned heroin, but not sucrose-seeking behaviour. Journal of Neurochemistry, 98: 905–915. doi: 10.1111/j.1471-4159.2006.03917.x
- Issue published online: 19 JUN 2006
- Article first published online: 19 JUN 2006
- Received August 31, 2005; revised manuscript received March 13, 2006; accepted March 28, 2006.
- drug abuse;
- gene expression;
- mesocorticolimbic targets;
Re-exposure to drug-related cues elicits drug-seeking behaviour and relapse in both humans and laboratory animals even after months of abstinence. Identifying neural and molecular substrates underlying conditioned heroin-seeking behaviour will be helpful in understanding mechanisms behind opiate relapse. In humans and animals, brain areas activated by natural reward-related stimuli (e.g. food, sex) do not show a complete overlap with those activated by stimuli associated with drugs of abuse, suggesting the involvement of different circuitry. To that end, we investigated neural reactivity by measuring immediate early gene (IEG) expression patterns in mesocorticolimbic system target areas following cue-induced reinstatement of heroin seeking and compared those IEG expression patterns to what was measured during natural reward (sucrose)-seeking behaviour. Animals were trained to administer heroin associated with a compound audio-visual cue. Re-exposure to the cue after 3 weeks of withdrawal reinstated heroin-seeking behaviour, which resulted in IEG expression of ania-3, MKP-1, c-fos and Nr4a3 in the medial prefrontal cortex (mPFC), and of ania-3 in the orbital frontal cortex (OFC) and nucleus accumbens core (NAC). The expression patterns for heroin-seeking behaviours did not generalize to sucrose-seeking behaviours, indicating that the two behaviours involve different connectivity pathways of neuronal signalling.