Ericka Peterson

Dopamine release in ventral striatum of pathological gamblers losing money

Linnet J, Peterson E, Doudet DJ, Gjedde A, Møller A. Dopamine release in ventral striatum of pathological gamblers losing money.

Inverse association between dopaminergic neurotransmission and Iowa Gambling Task performance in pathological gamblers and healthy controls

The dopamine system is believed to affect gambling behavior in pathological gambling. Particularly, dopamine release in the ventral striatum appears to affect decision-making in the disorder. This study investigated dopamine release in the ventral striatum in relation to gambling performance on the Iowa Gambling Task (IGT) in 16 Pathological Gamblers (PG) and 14 Healthy Controls (HC). We used Positron Emission Tomography (PET) to measure the binding potential of [(11)C] raclopride to dopamine D2/3 receptors during a baseline and gambling condition. We hypothesized that decreased raclopride binding potentials in the ventral striatum during gambling (indicating dopamine release) would be associated with higher IGT performance in Healthy Controls, but lower IGT performance in Pathological Gamblers. The results showed that Pathological Gamblers with dopamine release in the ventral striatum had significantly lower IGT performance than Healthy Controls. Furthermore, dopamine release was associated with significantly higher IGT performance in Healthy Controls and significantly lower IGT performance in Pathological Gamblers. The results suggest that dopamine release is involved both in adaptive and maladaptive decision-making. These findings may contribute to a better understanding of dopaminergic dysfunctions in pathological gambling and substance related addictions.

Striatal dopamine release codes uncertainty in pathological gambling

Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand, dopamine release coded uncertainty, we would find an inversely U-shaped function. The data supported an inverse U-shaped relation between striatal dopamine release and IGT performance if the pathological gambling group, but not in the healthy control group. These results are consistent with the hypothesis of dopaminergic sensitivity toward uncertainty, and suggest that dopaminergic sensitivity to uncertainty is pronounced in pathological gambling, but not among non-gambling healthy controls. The findings have implications for understanding dopamine dysfunctions in pathological gambling and addictive behaviors.

Pathological gambling: relation of skin conductance response to dopaminergic neurotransmission and sensation-seeking.

Absent Skin Conductance Response (SCR) in pathological gambling (PG) may relate to dopaminergic mechanisms. We recruited equal numbers of PG subjects and healthy control (HC) subjects, and then tested the claim that SCR is less conditioned by dopaminergic activity in PG subjects. During active gambling, SCR differed in PG and HC subjects (P < 0.05), but positron emission tomography revealed the same dopamine receptor availability. However, highly sensation-seeking (HS) PG subjects had lower dopamine receptor availability (P < 0.0001) in the baseline, compared to normal sensation-seeking (NS) PG subjects. We find that HS versus NS controls had the same observation of significant increase of binding potential (BP(ND)) in high compared to normal sensation seekers. In both groups, PG and HC, highly sensation-seeking subjects had significant increase of receptor availability in striatum, compared to normally sensation-seeking subjects, separately (P < 0.05 and P = 0.02, respectively) and together (P < 0.0005). We conclude that SCR is less conditioned by dopaminergic activity in highly sensation-seeking subjects, regardless of PG status.

Variable ATP Yields and Uncoupling of Oxygen Consumption in Human Brain

The distribution of brain oxidative metabolism values among healthy humans is astoundingly wide for a measure that reflects normal brain function and is known to change very little with most changes of brain function. It is possible that the part of the oxygen consumption rate that is coupled to ATP turnover is the same in all healthy human brains, with different degrees of uncoupling explaining the variability of total oxygen consumption among people. To test the hypothesis that about 75% of the average total oxygen consumption of human brains is common to all individuals, we determined the variability in a large group of normal healthy adults. To establish the degree of variability in different regions of the brain, we measured the regional cerebral metabolic rate for oxygen in 50 healthy volunteers aged 21-66 and projected the values to a common age of 25.Within each subject and region, we normalized the metabolic rate to the population average of that region. Coefficients of variation ranged from 10 to 15% in the different regions of the human brain and the normalized regional metabolic rates ranged from 70% to 140% of the population average for each region, equal to a two-fold variation. Thus the hypothetical threshold of oxygen metabolism coupled to ATP turnover in all subjects is no more than 70% of the average oxygen consumption of that population.