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Increases in dopamine and glutamate transmission in the nucleus accumbens independently promote the reinstatement of cocaine seeking, an animal model of relapse. Here we have tested whether cocaine reinstatement in rats depends on interactions between accumbal dopamine and glutamate systems that are mediated by Ca(2+)/calmodulin-mediated kinase II (CaMKII).(More)
Major depressive disorder (MDD) is characterized by structural and neurochemical changes in limbic structures, including the hippocampus, that regulate mood and cognitive functions. Hippocampal atrophy is observed in patients with depression and this effect is blocked or reversed by antidepressant treatments. Brain-derived neurotrophic factor and other(More)
Cocaine self-administration alters patterns of gene expression in the brain that may underlie cocaine-induced neuronal plasticity. In the present study, male Sprague Dawley rats were allowed to self-administer cocaine (0.25 mg/infusion) 2 h/d for 14 d, followed by 7 d of forced abstinence. Compared with yoked saline control rats, cocaine self-administration(More)
The lifetime prevalence (∼16%) and the economic burden ($100 billion annually) associated with major depressive disorder (MDD) make it one of the most common and debilitating neurobiological illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology of MDD have not been identified. Here we use whole-genome expression(More)
Cocaine addiction in human addicts is characterized by a high rate of relapse following successful detoxification. Relapse to drug taking/seeking can be precipitated by several stimuli including, but not limited to, re-exposure to cocaine itself. In order to understand the mechanisms underlying cocaine craving, a substantial effort has been devoted to(More)
Accumulating evidence suggests that metabotropic glutamate receptors (mGluRs) are involved in both cocaine reinforcement and the reinstatement of cocaine-seeking behavior. In the present experiments, rats were trained to self-administer cocaine under fixed ratio (for cocaine priming-induced reinstatement) or second-order (for cocaine cue-induced(More)
Major depressive disorder (MDD) is a heterogeneous illness for which there are currently no effective methods to objectively assess severity, endophenotypes, or response to treatment. Increasing evidence suggests that circulating levels of peripheral/serum growth factors and cytokines are altered in patients with MDD, and that antidepressant treatments(More)
The direct glutamatergic projection from the medial prefrontal cortex (mPFC) to the nucleus accumbens plays a critical role in mediating the reinstatement of cocaine seeking behavior. The mPFC also sends glutamatergic projections to the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDT), which in turn send glutamatergic and(More)
We delineated a heritable phenotype resulting from the self-administration of cocaine in rats. We observed delayed acquisition and reduced maintenance of cocaine self-administration in male, but not female, offspring of sires that self-administered cocaine. Brain-derived neurotrophic factor (Bdnf) mRNA and BDNF protein were increased in the medial(More)
A growing body of evidence indicates that enhanced AMPA-mediated glutamate transmission in the core of the nucleus accumbens is critically involved in cocaine priming-induced reinstatement of drug seeking, an animal model of relapse. However, the extent to which increased glutamate transmission in the other major subregion of the nucleus accumbens, the(More)