The Orbitofrontal Cortex Regulates Outcome-Based Decision-Making via the Lateral Striatum.

The orbitofrontal cortex regulates outcome-based decision-making via the lateral striatum.

Eur J Neurosci. 2013 May 8;
Gourley SL, Olevska A, Zimmermann KS, Ressler KJ, Dileone RJ, Taylor JR

The orbitofrontal cortex (oPFC) sends substantial projections to the ventrolateral striatum and aspects of the nucleus accumbens that are, functionally, poorly understood. This is despite probable cortico-striatal involvement in multiple diseases such as addiction and obsessive-compulsive disorder. Here we surgically disconnected the oPFC from the ventrolateral striatum using unilateral asymmetric lesions in mice and classified instrumental decision-making strategies. Mice with symmetric lesions that spared one oPFC-striatal network served as controls. As a complementary approach, we selectively knocked down Brain-derived neurotrophic factor (Bdnf) bilaterally in the oPFC and ascertained behavioral and neurobiological consequences within the downstream striatum. oPFC-striatal disconnection and oPFC Bdnf knockdown blocked sensitivity to outcome-predictive relationships in both food-reinforced and cocaine-associated settings. Bdnf knockdown simultaneously regulated striatal BDNF expression, and striatal c-Fos predicted sensitivity to action-outcome associative contingencies. Previous evidence strongly implicates the dorsolateral striatum in stimulus-response habit formation. Our findings thus provide novel evidence for functional compartmentalisation within the lateral striatum, with the dorsal compartment subserving classical stimulus-response habit systems and a ventral compartment coordinating outcome-based decision-making via oPFC interactions. This compartmentalisation may apply to both ‘natural’, as in the case of food-reinforced behavior, and ‘pathological’, as in the case of cocaine-seeking, contexts. HubMed – addiction


‘Ecstasy’ and the use of sleep medications in a general community sample: a 4-year follow-up.

Addiction. 2013 May 7;
Tait RJ, George A, Olesen S

AIMS: Animal models show that a single dose of 3,4-methylenedioxymethamhetamine (MDMA; ‘ecstasy’) can result in long-term disruption of sleep. We evaluated the relationship between ecstasy consumption and the use of sleep medications in humans after controlling for key factors. DESIGN: The Personality and Total Health Through Life project uses a longitudinal cohort with follow-up every 4 years. This study reports data from waves 2 and 3. SETTING: Participants were recruited from the electoral roll in the Australian Capital Territory and Queanbeyan, New South Wales, Australia. PARTICIPANTS: Participants were aged 20-24 years at wave 1 (1999-2000). MEASURES: The study collected self-reported data on ecstasy, meth/amphetamine, cannabis, alcohol, tobacco and use of sleeping medications (pharmaceutical or other substances). Depression was categorized using the Brief Patient Health Questionnaire (BPHQ). Other psychosocial measures included life-time traumas. We used generalized estimating equations to model outcomes. FINDINGS: Ecstasy data were available from 2128 people at wave 2 and 1977 at wave 3: sleeping medication use was reported by 227 (10.7%) respondents at wave 2 and 239 (12.1%) at wave 3. Increased odds ratios (OR) for sleeping medication use was found for those with depression [OR?=?1.88, 95% confidence interval (CI): 1.39, 2.53], women (OR?=?1.44, 95% CI: 1.13, 1.84), and increased by 19% for each life-time trauma. Ecstasy use was not a significant predictor, but ?monthly versus never meth/amphetamine use increased the odds (OR?=?3.03, 95% CI 1.30, 7.03). CONCLUSION: The use of ecstasy appears to be associated with the use of sleeping medications but this association can be accounted for by other factors. HubMed – addiction


Measurement invariance of DSM-IV alcohol, marijuana and cocaine dependence between community-sampled and clinically overselected studies.

Addiction. 2013 May 7;
Derringer J, Krueger RF, Dick DM, Agrawal A, Bucholz KK, Foroud T, Grucza RA, Hesselbrock MN, Hesselbrock V, Kramer J, Nurnberger JI, Schuckit M, Bierut LJ, Iacono WG, McGue M

AIMS: To examine whether DSM-IV symptoms of substance dependence are psychometrically equivalent between existing community-sampled and clinically overselected studies. PARTICIPANTS: A total of 2476 adult twins born in Minnesota and 4121 unrelated adult participants from a case-control study of alcohol dependence. MEASUREMENTS: Life-time DSM-IV alcohol, marijuana and cocaine dependence symptoms and ever use of each substance. DESIGN: We fitted a hierarchical model to the data, in which ever use and dependence symptoms for each substance were indicators of alcohol, marijuana or cocaine dependence which were, in turn, indicators of a multi-substance dependence factor. We then tested the model for measurement invariance across participant groups, defined by study source and participant sex. FINDINGS: The hierarchical model fitted well among males and females within each sample [comparative fit index (CFI)?>?0.96, Tucker-Lewis index (TLI)?>?0.95 and root mean square error of approximation (RMSEA)?HubMed – addiction



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