Imaging Dopamine Transmission in the Frontal Cortex: A Simultaneous Microdialysis and [(11)C]FLB 457 PET Study.

Imaging dopamine transmission in the frontal cortex: a simultaneous microdialysis and [(11)C]FLB 457 PET study.

Mol Psychiatry. 2013 Feb 26;
Narendran R, Jedema HP, Lopresti BJ, Mason NS, Gurnsey K, Ruszkiewicz J, Chen CM, Deuitch L, Frankle WG, Bradberry CW

In a recent human positron emission tomography (PET) study we demonstrated the ability to detect amphetamine-induced dopamine (DA) release in the prefrontal cortex as a reduction in the binding of the DA D(2/3) radioligand [(11)C]FLB 457. A key requirement for validating this paradigm for use in clinical studies is demonstrating that the changes in [(11)C]FLB 457 binding observed with PET following amphetamine are related to changes in dialysate DA concentration as measured with microdialysis. Microdialysis and PET experiments were performed to compare, in five rhesus monkeys, amphetamine-induced DA release and [(11)C]FLB 457 displacement in the frontal cortex after three doses of amphetamine (0.3?mg?kg(-1), 0.5?mg?kg(-1) and 1.0?mg?kg(-1)). Amphetamine led to a significant dose-dependent increase in dialysate (0.3?mg?kg(-1): 999±287%; 0.5?mg?kg(-1): 1320±432%; 1.0?mg?kg(-1): 2355±1026%) as measured with microdialysis and decrease in [(11)C]FLB 457 binding potential (BP(ND,) 0.3?mg?kg(-1): -6±6%; 0.5?mg?kg(-1): -16±4%; 1.0?mg?kg(-1): -24±2%) as measured with PET. The relationship between amphetamine-induced peak ?DA and ?[(11)C]FLB 457 BP(ND) in the frontal cortex was linear. The results of this study clearly demonstrate that the magnitude of dialysate DA release is correlated with the magnitude of the reduction in [(11)C]FLB 457 BP(ND) in the frontal cortex. The use of the [(11)C]FLB 457-amphetamine imaging paradigm in humans should allow for characterization of prefrontal cortical DA release in neuropsychiatric disorders such as schizophrenia and addiction.Molecular Psychiatry advance online publication, 26 February 2013; doi:10.1038/mp.2013.9. HubMed – addiction

Individual variation in resisting temptation: implications for addiction.

Neurosci Biobehav Rev. 2013 Feb 21;
Saunders BT, Robinson TE

When exposed to the sights, sounds, smells and/or places that have been associated with rewards, such as food or drugs, some individuals have difficulty resisting the temptation to seek out and consume them. Others have less difficulty restraining themselves. Thus, Pavlovian reward cues may motivate maladaptive patterns of behavior to a greater extent in some individuals than in others. We are just beginning to understand the factors underlying individual differences in the extent to which reward cues acquire powerful motivational properties, and therefore, the ability to act as incentive stimuli. Here we review converging evidence from studies in both human and non-human animals suggesting that a subset of individuals are more “cue reactive”, in that certain reward cues are more likely to attract these individuals to them and motivate actions to get them. We suggest that those individuals for whom Pavlovian reward cues become especially powerful incentives may be more vulnerable to impulse control disorders, such as binge eating and addiction. HubMed – addiction

From the ventral to the dorsal striatum: devolving views of their roles in drug addiction.

Neurosci Biobehav Rev. 2013 Feb 21;
Everitt BJ, Robbins TW

We revisit our hypthesis that drug addiction can be viewed as the endpoint of a series of transitions from initial voluntarily drug use to habitual, and ultimately compulsive drug use. We especially focus on the transitions in striatal control over drug seeking behaviour that underlie these transitions since functional heterogeneity of the striatum was a key area of Ann Kelley’s research interests and one in which she made enormous contributions. We also discuss the hypothesis in light of recent data that the emergence of a compulsive drug seeking habit both reflects a shift to dorsal striatal control over behaviour and impaired prefontal cortical inhibitory control mechanisms. We further discuss aspects of the vulnerability to compulsive drug use and in particular the impact of impulsivity. In writing this review we acknowledge the untimely death of an outstanding scientist and a dear personal friend. HubMed – addiction

A high physical symptom count reduces the effectiveness of treatment for depression, independently of chronic medical conditions.

J Psychosom Res. 2013 Mar; 74(3): 179-85
Huijbregts KM, de Jong FJ, van Marwijk HW, Beekman AT, Adèr HJ, van der Feltz-Cornelis CM

To assess to what extent a high physical symptom count influences the effect of treatment for major depressive disorder (MDD), and whether or not actual comorbid medical conditions explain this relationship.Secondary data-analysis on a cluster-randomized trial in primary care, comparing the effectiveness of collaborative care with care as usual (CAU). MDD was measured using the PHQ-9. The Physical Symptoms Questionnaire (PSQ) was filled out at baseline by 115 patients (77.2% of those who entered the trial). Multilevel logistic regression models were used to test whether a high physical symptom count predicted lack of response to treatment, adding interaction terms to test differential effects on collaborative care versus CAU.A high physical symptom count negatively influenced the effect of both collaborative care and care as usual (no interaction). Specifically, a high physical symptom count predicted lack of response in both conditions at 3 (odds ratio=6.8), 6 (OR=4.1), and 9months follow-up (OR=6.4). This was not explained by chronic physical illness.In this RCT, patients with MDD accompanied by a high physical symptom count benefited less from treatment for MDD in primary care, regardless of the type of treatment (either collaborative care or CAU). This was not explained by the presence of comorbid medical conditions. Further research is needed to improve treatment for MDD accompanied by a high physical symptom count, although collaborative care for depression is still more effective than CAU for this group of patients. Trial registration: Dutch trial register ISRCTN15266438. HubMed – addiction

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