Abstract
Rationale
The motivational process that regulates approach behavior toward salient distal stimuli (i.e., incentive motivation) plays a key role in voluntary behavior and motivational disorders such as addiction. This process may be mediated by many neurotransmitter systems and a network of many brain structures, including the median and dorsal raphe regions (MR and DR, respectively).
Objective
We sought to examine whether the blockade of excitatory amino acid receptors in the MR and DR is rewarding, using intracranial self-administration, and whether the self-administration effect can be explained by drug’s effectiveness to enhance incentive motivation, using a visual sensation seeking procedure.
Results
Rats learned to self-administer the AMPA receptor antagonist ZK 200775 into the vicinity of the MR, DR, or medial oral pontine reticular regions, but not the ventral tegmental area. The NMDA receptor antagonist AP5 was also self-administered into the MR, while it was not readily self-administered into other regions. When ZK 200775 was noncontingently administered into the MR, rats markedly increased approach responses rewarded by brief illumination of a light stimulus. In addition, contingent administration of ZK 200775 into the MR induced a conditioning effect on approach responses.
Conclusions
Rats self-administer excitatory amino acid receptor antagonists into the MR and adjacent regions. Self-administration effect of AMPA receptor antagonists into the MR can be largely explained by the manipulation’s properties to invigorate ongoing approach behavior and induces conditioned approach. Glutamatergic afferents to the median raphe and adjacent regions appear to tonically suppress incentive-motivational processes.
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Acknowledgments
This work was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. We would like to thank Drs. Anton Ilango and Dong Wang for their comments on earlier versions of the manuscript.
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We do not have any conflict of interest or financial compensation to disclose.
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Webb, S.M., Vollrath-Smith, F.R., Shin, R. et al. Rewarding and incentive motivational effects of excitatory amino acid receptor antagonists into the median raphe and adjacent regions of the rat. Psychopharmacology 224, 401–412 (2012). https://doi.org/10.1007/s00213-012-2759-0
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DOI: https://doi.org/10.1007/s00213-012-2759-0