Dopamine release in the prefrontal cortex increases flattening of the glucocorticoid rhythm, which may underpin prefrontal dysfunction in bipolar disorder patients, conclude researchers.

Previous studies have shown that bipolar disorder patients have abnormal glucocorticoid secretion, dopaminergic neurotransmission, and prefrontal cortex function, explain Sarah Gartside, from Newcastle University in the UK, and colleagues.

Believing that flattening of the diurnal glucocorticoid rhythm, which is common in bipolar disorder, modulates dopaminergic transmission in the prefrontal cortex, leading to functional abnormalities, the team administered corticosterone 50 µg/ml or 0.5% ethanol vehicle to the drinking water of male rats for 13??”15 days.

Compared with animals given vehicle, those treated with corticosterone had a flattened diurnal rhythm in blood corticosterone concentrations, with levels significantly lower before the diurnal peak and significantly higher at the nadir of the rhythm, and significant adrenal gland atrophy.

Corticosterone-treated animals had significantly increased basal dopamine levels compared with those given vehicle, the team reports in the journal Neuropsychopharmacology. Analysis revealed that depolarization-evoked release was also enhanced, while local blockade of terminal D2 autoreceptors failed to normalize release to control values.

In the ventral tegmental area, levels of mRNAs coding tyrosine hydroxylase and the vesicular monoamine transporter 2, as measured using in situ hybridization, were significantly increased in rats treated with corticosterone compared with vehicle-treated rats.

“The finding of increased dopamine release in the prefrontal cortex suggests a causal link between the neuroendocrine abnormalities observed in mood disorders, and some of the cognitive symptoms of these conditions: the prefrontal cortex plays a key role in cognitive functions including working memory, selective attention, goal directed behavior, and behavioral inhibition with prefrontal dopaminergic neurotransmission strongly influencing these functions,” the researchers write.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Free abstract

• ">
• Buy Seroquel Online
• Brain activity determines risk or resilience in bipolar disorder
• Young Adults May Outgrow Bipolar Disorder