Astrid van Irsen1, Tess Kool2, Anouk Corstens3, Margarita Mita4, Djo de Lange5, Margo Slomp6, Andries Kalsbeek7, Susanne la Fleur8
(1) Amsterdam UMC location University of Amsterdam, Endocrinology Laboratory, Dept Clin Chemistry, Meibergdreef 9, Amsterdam, The Netherlands. (2) Amsterdam UMC location University of Amsterdam, Endocrinology Laboratory, Dept Clin Chemistry, Meibergdreef 9, Amsterdam, The Netherlands. (3) Amsterdam UMC location University of Amsterdam, Endocrinology Laboratory, Dept Clin Chemistry, Meibergdreef 9, Amsterdam, The Netherlands. (4) Amsterdam UMC location University of Amsterdam, Endocrinology Laboratory, Dept Clin Chemistry, Meibergdreef 9, Amsterdam, The Netherlands. (5) Amsterdam UMC location University of Amsterdam, Endocrinology Laboratory, Dept Clin Chemistry, Meibergdreef 9, Amsterdam, The Netherlands. (6) Amsterdam UMC location University of Amsterdam, Endocrinology Laboratory, Dept Clin Chemistry, Meibergdreef 9, Amsterdam, The Netherlands. (7) Amsterdam UMC location University of Amsterdam, Endocrinology Laboratory, Dept Clin Chemistry, Meibergdreef 9, Amsterdam, The Netherlands. (8) Amsterdam UMC location University of Amsterdam, Endocrinology Laboratory, Dept Clin Chemistry, Meibergdreef 9, Amsterdam, The Netherlands.
The nucleus accumbens (NAc) plays a critical role in reward and food-motivated behavior. It contains a core that is surrounded by a medial and lateral shell. The majority of accumbalneurons consists of medium spiny neurons (MSNs), which nearly all either express dopamine D1 receptors (Drd1) or dopamine D2 (Drd2) receptors. Previous findings showed that in rats deep brain stimulation of the NAc medial shell (mshNAc) increased blood glucose and plasma glucagon concentrations compared to sham or core stimulation. Moreover, infusion of vanoxerine, a dopamine reuptake inhibitor, into the mshNAc of rats decreased endogenous glucose production, blood glucose and plasma glucagon concentrations compared to vehicle. These effects may seem contradictory, however, this can likely be explained by the opposing effects of Drd1 and Drd2 activation under different conditions and their distinctive projections. Based on previous viral tracer experiments in rats (unpublished), we know mshNAc MSNsDrd1 mainly project to the lateral hypothalamic area (LHA).
To determine the role of this mshNAcDrd1>LHA connection in glucose metabolism, we employed chemogenetics in Drd1-Cre transgenic male rats to target MSNsDrd1 in the mshNAc. We compared overall activation of MSNsDrd1 in the mshNAc to specific activation of the mshNAcDrd1>LHA connection, on glucose tolerance. Activation of the mshNAcDrd1>LHA connection improved glucose tolerance (drug effect p<0.05 and interaction effect drug x time p<0.01, n=9), whereas overall mshNAc MSNDrd1 activation did not result in a significant effect. Overall, these results increase our understanding of neural circuitry underlying glucose metabolism. Currently we are replicating this experiment in female rats, but interestingly they seem to show distinct results