Articles: nucleus-accumbens-drug-effects.
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Synaptic alterations in the nucleus accumbens (NAc) are crucial for the aberrant reward-associated learning that forms the foundation of drug dependence. Altered glutamatergic synaptic plasticity, in particular, is thought to be a vital component of the neurobiological underpinnings of addictive behavior. The development of bacterial artificial chromosome-eGFP (enhanced green fluorescent protein) transgenic mice that express eGFP driven by endogenous D1 dopamine receptor (D1R) promoters has now allowed investigation of the cell type-specific synaptic modifications in the NAc in response to drugs of abuse. ⋯ Complete recovery of the baseline plasticity phenotype in both cell types required a full 2 weeks of withdrawal from CIE vapor exposure. Thus, we observed a cell type specificity of synaptic plasticity in the NAc shell, as well as, a gradual recovery of the pre-ethanol exposure plasticity state following extended withdrawal. These changes highlight the adaptability of NAc shell MSNs to the effects of ethanol exposure and may represent critical neuroadaptations underlying the development of ethanol dependence.
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Nature neuroscience · Sep 2014
Cocaine exposure reorganizes cell type- and input-specific connectivity in the nucleus accumbens.
Repeated exposure to cocaine alters the structural and functional properties of medium spiny neurons (MSNs) in the nucleus accumbens (NAc). These changes suggest a rewiring of the NAc circuit, with an enhancement of excitatory synaptic connections onto MSNs. However, it is unknown how drug exposure alters the balance of long-range afferents onto different cell types in the NAc. ⋯ We also found that amygdala activity was required for cocaine-induced changes to behavior and connectivity. Finally, we established how heightened amygdala innervation can explain the structural and functional changes evoked by cocaine. Our findings reveal how exposure to drugs of abuse fundamentally reorganizes cell type- and input-specific connectivity in the NAc.
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Pharmacol. Biochem. Behav. · Sep 2014
The microinjection of a cannabinoid agonist into the accumbens shell induces anxiogenesis in the elevated plus-maze.
This study investigated the effect of a cannabinoid agonist injected into the shell region of the nucleus accumbens (nAcb shell) on anxiety-related behaviors. The animals (male Wistar rats) were unilaterally microinjected with either ACEA (arachidonyl-2'-chloroethylamide a CB1 receptor agonist) at doses of 0.005, 0.05 or 0.5 pmol, or vehicle (ethanol 0.04% in saline 0.9%) and submitted to the elevated plus-maze (EPM), a pre-clinical test of anxiety. ⋯ The locomotor activity was not changed at the dose of 0.05 pmol ACEA microinjected into the nAcb shell. The present data suggest that activation of cannabinoid receptors in the nAcb shell may modulate fear/anxiety in the EPM.
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The partial opioid agonist thienorphine is currently in Phase II clinical trials in China as a candidate drug for the treatment of opioid dependence. However, its effect on synaptic plasticity in the NAc (nucleus accumbens) remains unclear. In the present study, we measured structural parameters of the synaptic interface to investigate the effect of thienorphine, morphine or a combination of both on synaptic morphology in the NAc of rats. ⋯ Furthermore, synaptophysin expression in the NAc was significantly greater after chronic administration of thienorphine, morphine, or both, than after saline. These results identified interesting differences between thienorphine and morphine in their effects on synaptic structure and synaptophysin expression in the rat NAc. Further study is deserved to investigate thienorphine as a new treatment for opioid dependence.