Neuroscience
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Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of non-selective rats triggered by environmental context. However, to date, there has been no research on the effects of D1 receptor agents on EtOH- seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. ⋯ Microinfusion of D1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats.
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Working memory (WM) impairment has received attention as a behavioral characteristic of schizophrenia. Neurobiological studies have led to the hypothesis that a deficit in dopamine transmission through D1 receptors in the prefrontal cortex (PFC) is associated with WM impairment in schizophrenia. However, empirical approaches that aim to clarify the nature of the impairment and its underlying mechanism are difficult to enact, especially in unmedicated patients. ⋯ Hypodopaminergic modulation resulted in imprecision and a reduced capacity in WM primarily due to decreased N-methyl-d-aspartate (NMDA) conductance. Increasing NMDA conductance ameliorated both impairments. These results account for the mechanism that underlies WM impairments in schizophrenia and provide a theoretical basis for combination therapy with antipsychotic drugs and drugs that enhance NMDA receptor function, which is expected to be effective for the treatment of WM impairments in these patients.
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We investigated phonological processing in normal readers to answer the question to what extent phonological recoding is active during silent reading and if or how it guides lexico-semantic access. We addressed this issue by looking at pseudohomophone and baseword frequency effects in lexical decisions with event-related functional magnetic resonance imaging (fMRI). ⋯ This baseword frequency effect was qualified by activation differences in bilateral angular and left supramarginal, and bilateral middle temporal gyri for pseudohomophones with low- compared to high-frequency basewords. We propose that lexical decisions to pseudohomophones involves phonology-driven lexico-semantic activation of their basewords and that this is converging neuroimaging evidence for automatically activated phonological representations during silent reading in experienced readers.
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Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. ⋯ Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model.
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Chronic ethanol consumption is known to downregulate expression of the major glutamate transporter 1 (GLT-1), which increases extracellular glutamate concentrations in subregions of the mesocorticolimbic reward pathway. While β-lactam antibiotics were initially identified as potent upregulators of GLT-1 expression, only ceftriaxone has been extensively studied in various drug addiction models. Therefore, in this study, adult male alcohol-preferring (P) rats exposed chronically to ethanol were treated with other β-lactam antibiotics, ampicillin, cefazolin or cefoperazone (100mg/kg) once daily for five consecutive days to assess their effects on ethanol consumption. ⋯ Cerebrospinal fluid concentrations of ampicillin, cefazolin or cefoperazone have been confirmed using high-performance liquid chromatography. These findings demonstrate that multiple β-lactam antibiotics demonstrate efficacy in reducing alcohol consumption and appear to be potential therapeutic compounds for treating alcohol abuse and/or dependence. In addition, these results suggest that pAKT may be an important player in this effect, possibly through increased transcription of GLT-1.