Browsing by keyword "prefrontal cortex"
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Binge Alcohol Drinking Alters Synaptic Processing of Executive and Emotional Information in Core Nucleus Accumbens Medium Spiny NeuronsThe nucleus accumbens (NAc) is a forebrain region mediating the positive-reinforcing properties of drugs of abuse, including alcohol. It receives glutamatergic projections from multiple forebrain and limbic regions such as the prefrontal cortex (PFCx) and basolateral amygdala (BLA), respectively. However, it is unknown how NAc medium spiny neurons (MSNs) integrate PFCx and BLA inputs, and how this integration is affected by alcohol exposure. Because progress has been hampered by the inability to independently stimulate different pathways, we implemented a dual wavelength optogenetic approach to selectively and independently stimulate PFCx and BLA NAc inputs within the same brain slice. This approach functionally demonstrates that PFCx and BLA inputs synapse onto the same MSNs where they reciprocally inhibit each other pre-synaptically in a strict time-dependent manner. In alcohol-naive mice, this temporal gating of BLA-inputs by PFCx afferents is stronger than the reverse, revealing that MSNs prioritize high-order executive processes information from the PFCx. Importantly, binge alcohol drinking alters this reciprocal inhibition by unilaterally strengthening BLA inhibition of PFCx inputs. In line with this observation, we demonstrate that in vivo optogenetic stimulation of the BLA, but not PFCx, blocks binge alcohol drinking escalation in mice. Overall, our results identify NAc MSNs as a key integrator of executive and emotional information and show that this integration is dysregulated during binge alcohol drinking.
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D-Amphetamine Rapidly Reverses Dexmedetomidine-Induced Unconsciousness in RatsD-amphetamine induces emergence from sevoflurane and propofol anesthesia in rats. Dexmedetomidine is an alpha2-adrenoreceptor agonist that is commonly used for procedural sedation, whereas ketamine is an anesthetic that acts primarily by inhibiting NMDA-type glutamate receptors. These drugs have different molecular mechanisms of action from propofol and volatile anesthetics that enhance inhibitory neurotransmission mediated by GABAA receptors. In this study, we tested the hypothesis that d-amphetamine accelerates recovery of consciousness after dexmedetomidine and ketamine. Sixteen rats (Eight males, eight females) were used in a randomized, blinded, crossover experimental design and all drugs were administered intravenously. Six additional rats with pre-implanted electrodes in the prefrontal cortex (PFC) were used to analyze changes in neurophysiology. After dexmedetomidine, d-amphetamine dramatically decreased mean time to emergence compared to saline (saline:112.8 +/- 37.2 min; d-amphetamine:1.8 +/- 0.6 min, p < 0.0001). This arousal effect was abolished by pre-administration of the D1/D5 dopamine receptor antagonist, SCH-23390. After ketamine, d-amphetamine did not significantly accelerate time to emergence compared to saline (saline:19.7 +/- 18.0 min; d-amphetamine:20.3 +/- 16.5 min, p = 1.00). Prefrontal cortex local field potential recordings revealed that d-amphetamine broadly decreased spectral power at frequencies < 25 Hz and restored an awake-like pattern after dexmedetomidine. However, d-amphetamine did not produce significant spectral changes after ketamine. The duration of unconsciousness was significantly longer in females for both dexmedetomidine and ketamine. In conclusion, d-amphetamine rapidly restores consciousness following dexmedetomidine, but not ketamine. Dexmedetomidine reversal by d-amphetamine is inhibited by SCH-23390, suggesting that the arousal effect is mediated by D1 and/or D5 receptors. These findings suggest that d-amphetamine may be clinically useful as a reversal agent for dexmedetomidine.
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Neural activations during self-related processing in patients with chronic pain and effects of a brief self-compassion training - A pilot studyChronic pain negatively affects psychological functioning including self-perception. Self-compassion may improve self-related functioning in patients with chronic pain but understanding of the neural mechanisms is limited. In this study, twenty patients with chronic low back pain read negative self-related situations and were instructed to be either self-reassuring or self-critical while undergoing fMRI. Patients rated their feelings of self-reassurance and self-criticism during each condition, and brain responses were contrasted with neutral instructions. Trait self-compassion measures (SCS) were also acquired. Brain activations during self-criticism and self-reassurance were localized to prefrontal, self- and emotion-processing areas, such as medial prefrontal cortex, dorsolateral prefrontal cortex (dlPFC), dorsal anterior cingulate cortex and posterior cingulate cortex. Self-reassurance resulted in more widespread and stronger activations relative to self-criticism. Patients then completed a brief self-compassion training (8 contact hours, 2 weeks home practice). Exploratory pre-post comparisons in thirteen patients found that feelings of self-criticism were significantly reduced and brain activations were greater in the anterior insula and prefrontal cortical regions such as dlPFC. Pre-post increases in dlPFC activation correlated with increased self-compassion (SCS), suggesting that early self-compassion skills might primarily target self-criticism via dlPFC upregulation. Future controlled studies on self-compassion training in chronic pain populations should extend these results.
