D.J.R. and B.K. contributed equally to this study.
The neural substrates of amphetamine conditioned place preference: implications for the formation of conditioned stimulus–reward associations
Article first published online: 16 OCT 2006
European Journal of Neuroscience
Volume 24, Issue 7, pages 2089–2097, October 2006
How to Cite
Rademacher, D. J., Kovacs, B., Shen, F., Napier, T. C. and Meredith, G. E. (2006), The neural substrates of amphetamine conditioned place preference: implications for the formation of conditioned stimulus–reward associations. European Journal of Neuroscience, 24: 2089–2097. doi: 10.1111/j.1460-9568.2006.05066.x
- Issue published online: 16 OCT 2006
- Article first published online: 16 OCT 2006
- Received 24 April 2006, revised 17 July 2006, accepted 19 July 2006
- basolateral amygdala;
- ventral pallidum
Associations formed between conditioned stimuli and drug reward are major contributors in human drug addiction. To better understand the brain changes that accompany this process, we used immunohistochemistry for c-Fos (a neuronal activity marker), synaptophysin (a marker for synaptogenesis) and tyrosine kinase B receptor (a neurotrophic factor receptor that mediates synaptic plasticity) to investigate the neural substrates of amphetamine-induced conditioned place preference in rats. Conditioned place preference was induced by both 1.0 mg/kg and 0.3 mg/kg doses of amphetamine. Furthermore, amphetamine conditioning increased the density of c-Fos-immunoreactive cells and these cells were fully colocalized with the tyrosine kinase B receptor in the dentate gyrus, CA1 field and basolateral amygdala. Amphetamine conditioning increased the density of synaptophysin-immunoreactive varicosities in all brain regions studied, except the nucleus accumbens shell and dorsolateral striatum. The degree of conditioned place preference was highly correlated with c-Fos-immunoreactive cell density in the basolateral amygdala and with the density of synaptophysin-immunoreactive varicosities in all mesolimbic regions studied. The latter correlation was particularly impressive for the ventral pallidum and basolateral amygdala. The formation of conditioned stimulus–amphetamine reward associations is accompanied by tyrosine kinase B receptor expression in the basolateral amygdala and dentate gyrus, CA1 and CA3 fields of the hippocampus. These data therefore suggest that the formation of conditioned stimulus–reward associations requires, at least in part, activation of amygdalar–hippocampal circuits.