Michel Verheij and Judith Homberg, theme Stress-related disorders, recently published in Biological Psychiatry.Cocaine dependence is a serious brain disorder that affects millions of people worldwide. People expressing low levels of the serotonin transporter (SERT) gene are at a higher risk of developing addiction. SERT is expressed in the cells of two distinct brain regions called the median raphe nucleus (MRN) and the dorsal raphe nucleus (DRN). By reducing the expression of SERT in these two brain regions in laboratory rats, Dr. Verheij and Dr. Homberg in collaboration with Dr. Contet and Dr. Koob (The Scripps Research Institute, USA) showed that SERT-induced changes in the consumption of cocaine depend on the brain region in which the expression of SERT was reduced. Reduced expression of SERT in MRN cells was found to increase the intake of cocaine when the consumption of the drug was low, whereas reduced expression of SERT in DRN cells increased the intake of cocaine when the consumption of the drug was high.
The SERT-containing cells of the MRN and DRN ‘talk’ to other brain cells containing the stress hormone CRF. The international research team also showed that the SERT-induced increase in cocaine intake observed in animals with a low consumption of the drug was accompanied by changes in the levels of CRF in the paraventricular nucleus of the hypothalamus (PVN). In contrast, the SERT-induced increase in cocaine intake observed in animals with a high consumption of the drug was accompanied by changes in CRF levels in the central amygdala (CeA).
This study shows that cocaine consumption is regulated by distinct brain circuits depending on the amount of cocaine that is taken. Based on their findings, the researchers hypothesize that the DRN-CeA circuit ‘overrules’ the MRN-PVN circuit when the drug intake shifts from low to high. These results also suggest that an increased reactivity of the CRF-containing cells within the two brain circuits may contribute to the higher risk of addiction in people expressing low levels of the SERT gene.
Michel Verheij Judith Homberg