New Insights into the Endocrine and Metabolic Roles of Dopamine D2 Receptors Gained from the <i>Drd2</i>^–/– Mouse

Abstract

Dopamine D2 receptor (D2R) participation in prolactin regulation is well documented, but the role of D2Rs in the control of other hormones involved in growth, food intake and glucose metabolism has not been extensively studied. The study of D2R knockout mice (Drd2^–/–) puts forward new insights into the role of the D2R in growth hormone (GH)-releasing hormone-GH regulation, peptides involved in food intake, glucose homeostasis, as well as in prolactinoma development. The expected phenotype of chronic hyperprolactinemia and prolactinoma development was found in the Drd2^–/– mouse, and this model constitutes a valuable tool in the study of dopamine-resistant prolactinomas. Unexpectedly, these mice were growth retarded, and the importance of functional hypothalamic D2Rs in the neonatal period was revealed. In the Drd2^–/– mouse there was a failure of high neonatal GH levels and therefore the expansion of pituitary somatotropes was permanently altered. These mice also had increased food intake, and a sexually dimorphic participation of the D2R in food intake regulation is suggested. The effect described is probably secondary to D2R regulation of prolactin secretion. Furthermore, the negative modulation of D2Rs on α-melanocyte-stimulating hormone release and positive action on the hypothalamic expression of orexins reveals the complex D2R regulation of food intake. Finally, pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development in the Drd2^–/– mouse may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. These results highlight the complex endocrine actions of the D2Rs at different levels, hypothalamus, pituitary or pancreas, which function to improve fitness, reproductive success and survival.

Activation of Dopamine D2 Receptor Is Critical for the Development of Form-Deprivation Myopia in the C57BL/6 Mouse

“…In the present study, mice lacking D2R were smaller and lighter, probably due to a decrease in food intake and/or dysfunction of the gastrointestinal system in the absence of D2R. 49 It should be noted that the smaller size of the body and eye in D2R KO mice may be linked, offering a partial nonvisual explanation to the refractive changes in these mice. Despite these limitations, a specific role of D2R in myopia development in these groups of animals could not be excluded.…”

Pituitary and Brain Dopamine D2 Receptors Regulate Liver Gene Sexual Dimorphism

“…Assessment of locomotor behavior of Drd2 -/-mice revealed a motor impairment, even though these mice did not show a compelling parkinsonian locomotor phenotype (23). But, as previously reported Drd2 -/-mice were hyperprolactinemic, growth retarded and had altered glucose metabolism (15,24,25). Fertility was reduced in female Drd2 -/-mice probably due to the high prolactin titers.…”

18F-Fallypride PET of Pancreatic Islets: In Vitro and In Vivo Rodent Studies

“…Imaging of peripheral dopamine receptors has not been pursued as vigorously, primarily because of a continually evolving understanding of their role in other disorders (20). The presence of significant levels of dopamine D 2 /D 3 Rs in the islet cells (9,21) and pancreatic tissue (22) provided the potential of a surrogate marker to study alterations in insulin secretion.…”