Homers regulate drug-induced neuroplasticity: implications for addiction - PubMed (original) (raw)

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Homers regulate drug-induced neuroplasticity: implications for addiction

Karen K Szumlinski et al. Biochem Pharmacol. 2008.

Abstract

Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

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Figures

Figure 1

Figure 1

Illustration of the putative interactions between (A) constitutively expressed (CC) Homer proteins and (B) IEG Homer proteins with their EVH1-bound partners within the postsynaptic density of dendritic spines.

Figure 2

Figure 2

Homer protein levels are differentially regulated in the cell body and terminal regions of the corticoaccumbens glutamate pathway by cocaine. Immunoblotting for total Homer protein expression was conducted on NAC and PFC tissue from C57BL/6J mice at 3 weeks withdrawal from repeated cocaine (7 X 30 mg/kg) or saline administration. Bottom panels: Anti-Homer1b/c and anti-Homer2a/b primary antibodies recognized bands at 47 kDa [e.g., 39,144,169,295]. Left: Cocaine-treated mice showed an approximately 50% reduction in Homer1b/c (t20=2.34, p=0.03) and Homer2a/b (t20=2.32, p=0.03] within the NAC. Right: Cocaine-treated mice did not differ from saline controls regarding Homer1b/c expression (p=0.95), but exhibited an approximately 30% increase in Homer2a/b (t20=2.45, p=0.02). *p<0.05 for saline versus cocaine.

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