We are examining how group 1 metabotropic glutamate receptors modify neuronal function and synaptic plasticity. This scientific goal is relevant to drug addiction since genetic deletion of mGluRS prevents neurobehavioral actions of cocaine Including behavioral activation and cocaine sensitization (Chiamulera et al., 2001). Moreover, mGluRS antagonists block behavioral responses to cocaine in rodents (Herzig and Schmidt, 2004) and primates (Lee et al., 2005;Paquet and Smith, 2003). One of our central hypotheses is that actions of mGIuR that are criticai for addition are transduced through the acton of a regulated adaptor system, that includes constitutively expressed Homer proteins together with an Immediate eariy gene fomn of Homer (H1 a). Homer proteins bind the C-terminus of group 1 metabotropic glutamate receptors as well as proteins that are down stream of mGluR in its various signaling pathways, and by self multimerization Homer can assemble these proteins into signaling complexes. The actions of Homer on mGluR signaling are complex and remari^ably elegant;Homer can regulate pharmacology of the receptor (Ango et al., 2001), the amplitude of the output and ability of the mGluR to receive convergent signals from dopamine receptors (DR) and growth factors including TritB. These pathways appear important for an understanding of the role of mGluR in addiction since genetic deletion of Homer results in enhanced sensitivity of mice to the addictive properties of cocaine
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