The neural substrates of amphetamine conditioned place preference: implications for the formation of conditioned stimulus-reward associations.

Full Abstract

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.

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Author information

Author/s: Rademacher, David J (DJ); Kovacs, Beatrix (B); Shen, Fei (F); Napier, T Celeste (TC); Meredith, Gloria E (GE);

Affiliation: Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.

Grants: DA016662 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: The European journal of neuroscience (Eur J Neurosci), published in France. (Language: eng)

Reference: 2006-Oct; vol 24 (issue 7) : pp 2089-97

Dates: Created 2006/10/27; Completed 2006/12/21; Revised 2007/12/03;

PMID: 17067306, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amphetamine - pharmacology
Animals
Behavior, Animal - drug effects
Brain - cytology
Cell Count - methods
Central Nervous System Stimulants - pharmacology
Conditioning, Operant - drug effects
Dose-Response Relationship, Drug
Immunohistochemistry - methods

Male
Neurons - drug effects; metabolism
Proto-Oncogene Proteins c-fos - metabolism
Rats
Rats, Sprague-Dawley
Receptor, trkB - metabolism
Reward
Synaptophysin - metabolism
Time Factors

Associated Chemicals: Central Nervous System Stimulants (0) ; Proto-Oncogene Proteins c-fos (0) ; Synaptophysin (0) ; Amphetamine (300-62-9) ; Receptor, trkB (EC 2.7.1.112)

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