Biological psychiatry
-
Biological psychiatry · May 2014
The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors.
The dynorphin (DYN)/kappa-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacologic manipulations. ⋯ Increased DYN A and increased KOR signaling could set the stage for a one-two punch during withdrawal that drives excessive alcohol consumption in alcohol dependence. Importantly, intracentral nucleus of the amygdala pharmacologic challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive alcohol consumption during withdrawal.
-
Biological psychiatry · May 2014
Nucleus accumbens neurons track behavioral preferences and reward outcomes during risky decision making.
To make appropriate decisions, organisms must evaluate the risks and benefits of action selection. The nucleus accumbens (NAc) has been shown to be critical for this processing and is necessary for appropriate risk-based decision-making behavior. However, it is not clear how NAc neurons encode this information to promote appropriate behavioral responding. ⋯ Consistent with previously demonstrated alterations in prospective reward value with effort and delay, NAc neurons encode information during reward-predictive cues and outcomes in a risk task that tracked the rats' preferred responses. This processing appears to contribute to subjective encoding of anticipated outcomes and thus may function to bias future risk-based decisions.
-
Biological psychiatry · May 2014
L-DOPA treatment selectively restores spine density in dopamine receptor D2-expressing projection neurons in dyskinetic mice.
L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia is an incapacitating complication of L-DOPA therapy that affects most patients with Parkinson's disease. Previous work indicating that molecular sensitization to dopamine receptor D1 (D1R) stimulation is involved in dyskinesias prompted us to perform electrophysiological recordings of striatal projection "medium spiny neurons" (MSN). Moreover, because enhanced D1R signaling in drug abuse induces changes in spine density in striatum, we investigated whether the dyskinesia is related to morphological changes in MSNs. ⋯ Chronic L-DOPA induces abnormal spine re-growth exclusively in D2R-MSNs and robust supersensitization to D1R-activated excitability in denervated striatal MSNs. These changes might constitute the anatomical and electrophysiological substrates of dyskinesia.
-
Biological psychiatry · May 2014
When optimism hurts: inflated predictions in psychiatric neuroimaging.
The ability to predict outcomes from neuroimaging data has the potential to answer important clinical questions such as which depressed patients will respond to treatment, which abstinent drug users will relapse, or which patients will convert to dementia. However, many prediction analyses require methods and techniques, not typically required in neuroimaging, to accurately assess a model's predictive ability. ⋯ We show via simulated data that models can appear predictive even when data and outcomes are random, and we note examples of optimistic prediction in the literature. We provide some recommendations for assessment of model performance.