Neuroscience
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The countermanding paradigm investigates the ability to withhold a response when a stop signal is presented occasionally. The race model (Logan and Cowan, 1984) was developed to account for performance in humans and to estimate the stop signal response time (SSRT). This model has yet to be fully validated for countermanding performance in rats. ⋯ Amphetamine (AMPH) (0.25, 0.5mg/kg) resulted in faster go trial RTs, baseline-dependent changes in SSRT and attenuated response adjustments. These findings demonstrate that the race model of countermanding performance, applied successfully in human and nonhuman primate models, can be employed in the countermanding performance of rodents. This is the first study to reveal response adjustments and AMPH-induced alterations of response adjustments in rodent countermanding.
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The Roman Low- and High-Avoidance rat strains (RLA-I vs RHA-I) have been bidirectionally selected and bred according to their performance in the two-way active avoidance response in the shuttle-box test. Numerous studies have reported a pronounced divergence in emotionality between the two rat strains including differences in novelty seeking, anxiety, stress coping, and susceptibility to addictive substances. However, the underlying molecular mechanisms behind these divergent phenotypes are not known. ⋯ To differentiate between mGlu2 and mGlu3 receptor protein levels, these were further studied using western blotting, which showed non-detectable levels of mGlu2 receptor protein in RHA rats, while no differences were observed for mGlu3 receptor protein levels. Collectively, these data show general congenital differences in the serotonergic system and a pronounced difference in mGlu2 receptor protein levels. We suggest that the differences in the serotonergic system may mediate some of the phenotypic characteristics in this strain such as hyper-impulsivity and susceptibility to drug addiction.
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Drug addiction behavior that is established and maintained by psychostimulants has been shown to be associated with the expression of brain-derived neurotrophic factor (BDNF) in the mesolimbic dopamine (DA) system. Cocaine has been used for most prior studies testing this effect of psychostimulants and therefore relatively little is known about its counterpart amphetamine (AMP). To fill this gap, the present study was designed to test whether BDNF mRNA expression levels in the DA terminal regions were changed specifically by d-AMP-induced conditioned place preference (CPP) followed by drug-primed reinstatement. ⋯ The BDNF mRNA level in the medial prefrontal cortex (mPFC) was significantly increased after the reinstatement, but not the CPP test. And, none of the other four assessed brain areas showed any change in BDNF mRNA level after d-AMP CPP or reinstatement. These findings support the notion that BDNF is involved in drug-seeking behavior and indicate that d-AMP reinstatement after extinction may be linked to an increase in BDNF mRNA expression in the mPFC.
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Increasing evidence has indicated that immune challenge by bacterial lipopolysaccharide (LPS) induces depressive-like behavior, neuroinflammatory response and upregulates phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP). However, whether the potential PDE4 inhibitor etazolate prevents the LPS-induced depressive-like behavior remains unclear. ⋯ Moreover, the antidepressant action of etazolate was paralleled by significantly reducing the expression levels of PDE4A, PDE4B, PDE4D and IL-1β and up-regulating the cAMP/phosphorylated cAMP response-element binding protein (pCREB)/brain-derived neurotrophic factor (BDNF) signaling in the hippocampus and prefrontal cortex of mice. These results indicate that the effects of etazolate on the depressive-like behavior induced by repeated LPS treatment may partially depend on the inhibition of PDE4 subtypes, the activation of the cAMP/pCREB/BDNF signaling and the anti-inflammatory responses in the hippocampus and prefrontal cortex.
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Whole-cell or cell-attached analysis was carried out in dopamine (DA) D2 receptor (D2R) knock-out (KO) mice to elucidate the function of this receptor in the regulation of GABAergic synaptic transmission onto striatal cholinergic interneurons as well as their spontaneous firing. In slice preparation obtained from wild-type mice, evoked GABAergic inhibitory postsynaptic currents (IPSCs) showed frequency-dependent suppression, and this suppression significantly decreased in the presence of a D2-like receptor antagonist or in D2R KO mice. ⋯ Spontaneous firing of striatal cholinergic interneurons was inhibited by 5- or 10-Hz stimulation, and the suppression was decreased in the presence of a D2-like receptor antagonist or in D2R KO mice. These findings substantiate the physiological role of D2R in the regulation of GABAergic synaptic transmission onto striatal cholinergic interneurons as well as their excitability, confirming the tight coupling between D2R and N-type calcium channels in the regulation of GABA release.