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The Journal of Neuroscience, August 20, 2008, 28(34):8406-8416; doi:10.1523/JNEUROSCI.1958-08.2008

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Behavioral/Systems/Cognitive
Dissociation between Rewarding and Psychomotor Effects of Opiates: Differential Roles for Glutamate Receptors within Anterior and Posterior Portions of the Ventral Tegmental Area

Maytal Shabat-Simon,^1,2 * Dino Levy,^1 * Alon Amir,¹ Moshe Rehavi,² and Abraham Zangen¹

¹Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel, and ²The Dr. Miriam and Sheldon G. Adelson Chair in the Biology of Addictive Diseases, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel

Correspondence should be addressed to Dr. Abraham Zangen, Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel. Email: a.zangen{at}weizmann.ac.il

The rewarding effects of drugs of abuse are thought to be dependent on the mesocorticolimbic dopamine system, which originates in the ventral tegmental area (VTA) and projects into the nucleus accumbens (NAC) and other forebrain regions. Heroin, by inhibiting GABAergic interneurons in the VTA, induces local dopaminergic activation and release in the NAC terminals. The role of other basic neurotransmitter systems, such as glutamate in the VTA, in mediating the rewarding effect of addictive drugs, is less established. We explored whether blockade of glutamate receptors in subregions of the VTA modulate the rewarding properties and/or the development of psychomotor changes induced by opiates. Administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; an AMPA/kainate receptor antagonist) into the anterior VTA blocked the rewarding effects of opiates in both the conditioned place preference and the self-administration paradigms without affecting the gradual increase of the psychomotor response to opiates. In contrast, administration of CNQX into the posterior VTA did not affect the rewarding properties of opiates, but blocked the initial sedative effect of opiates and the gradual increase of the psychomotor response to the drug. These findings suggest a critical role for glutamate receptors in the VTA in opiate reward, as well as behavioral and anatomical dissociation between the rewarding and psychomotor effects of opiates.

Key words: heroin; addiction; self-administration; conditioned place preference; sensitization; reward; glutamate; ventral tegmental area

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Received Dec. 28, 2007; revised July 6, 2008; accepted July 6, 2008.

Correspondence should be addressed to Dr. Abraham Zangen, Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel. Email: a.zangen{at}weizmann.ac.il

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