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Together, the above studies support a role for NMDA receptors in the rewarding effects of cocaine, nicotine and alcohol. Blockade of glutamate transmission via mGlu receptors also attenuated the rewarding effects of drugs of abuse. Caille and Parsons, The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring P rats.

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Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release. The role of mGlu7 receptors in nicotine and heroin reward remains to be investigated. Consequently, modulation of glial function may be able to attenuate the rewarding effects of drugs of abuse. The VTA receives extensive glutamatergic inputs from different limbic, cortical, and subcortical nuclei, such as the amygdala, PFC, lateral habenula, lateral hypothalamus, ventral pallidum, medial septum, septofimbrial nucleus, and ventrolateral bed nucleus of the stria terminalis Geisler and Zahm, . Geisler and Wise, . Watabe-Uchida et al.

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Therefore, one way to reduce glutamate transmission to attenuate the rewarding effects of drugs of abuse could be via exploitation of heterooligomeric complexes formed between glutamate and non-glutamate receptors or ion channels Duncan and Lawrence, Therefore, the increase in glutamate in response to high drug doses possibly suggests neurotoxic effects rather than rewarding effects. Mice lacking metabotropic glutamate receptor 4 do not show the motor stimulatory effect of ethanol. Intracranial self-administration of cocaine within the posterior ventral tegmental area of Wistar rats.

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