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Opiate tolerance by heroin self‐administration: An fMRI study in rat
Author(s) -
Xi ZhengXiong,
Wu Gaohong,
Stein Elliot A.,
Li ShiJiang
Publication year - 2004
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.20119
Subject(s) - nucleus accumbens , heroin , prefrontal cortex , thalamus , opiate , caudate nucleus , medicine , neuroscience , psychology , cingulate cortex , anterior cingulate cortex , mesolimbic pathway , anesthesia , pharmacology , ventral tegmental area , dopamine , central nervous system , drug , cognition , receptor , dopaminergic
Functional MRI (fMRI) was employed to determine whether repeated heroin self‐administration (SA) produces tolerance or sensitization in the brain of heroin‐SA rats. Twelve rats were evenly divided into saline and heroin (0.06 mg/kg, 4 hr/day) SA groups. There was a progressive increase in drug‐SA behavior and daily heroin intake during the 8–9 days of heroin‐SA training. Within 24 hr after the last session of daily SA, acute heroin (0.1 mg/kg) administration induced regional blood oxygen level‐dependent (BOLD) signals in both groups of rats. The positive BOLD signals appeared mainly in the cortical regions, including the prefrontal cortex, cingulate, and olfactory cortex, while the negative BOLD signals were predominantly located in subcortical regions such as caudate and putamen, nucleus accumbens, thalamus, and hypothalamus. However, the number of activated voxels or BOLD‐signal intensity was significantly less in heroin‐SA rat in regions of prefrontal cortex, nucleus accumbens, and thalamus, etc., compared to the changes in the saline control rats. Application of γ‐vinyl GABA (100 mg/kg), an irreversible GABA‐transaminase inhibitor, failed to block opiate actions in the heroin‐SA rats. Together, these data suggest that repeated heroin‐SA produces tolerance or desensitization of opiate actions in the rat brain, which may in turn potentiate drug SA behavior and drug intake. Magn Reson Med 52:108–114, 2004. © 2004 Wiley‐Liss, Inc.