Augmented D-1 dopamine receptor signaling and immediate-early gene induction in adult striatum after prenatal cocaine

作者：Tropea Thomas F; Guerriero Rejean M; Willuhn Ingo; Unterwald Ellen M; Ehrlich Michelle E; Steiner Heinz; Kosofsky Barry E^*

来源：Biological Psychiatry, 2008, 63(11): 1066-1074.

DOI：10.1016/j.biopsych.2007.12.002

• brain development
• D-1
• homer 1
• immediate-early genes
• prenatal cocaine
• zif 268

Background: Prenatal exposure to cocaine can impede normal brain development, triggering a range of neuroanatomical and behavioral anomalies that are evident throughout life. Mouse models have been especially helpful in delineating neuro-teratogenic consequences after prenatal exposure to cocaine. The present study employed a mouse model to investigate alterations in D-1 dopamine receptor signaling and downstream immediate-early gene induction in the striatum of mice exposed to cocaine in utero.
Methods: Basal, forskolin-, and D-1 receptor agonist-induced cyclic adenosine monophosphate (cAMP) levels were measured ex vivo in the adult male striatum in mice exposed to cocaine in utero. Further studies assessed cocaine-induced zif 268 and homer I expression in the striatum of juvenile (P15), adolescent (P36), and adult (P60) male mice.
Results: The D-1 dopamine receptor agonist SKF82958 induced significantly higher levels of cAMP in adult male mice treated with cocaine in utero compared with saline control subjects. No effects of the prenatal treatment were found for cAMP formation induced by forskolin. After an acute cocaine challenge (15 mg/kg, IP), these mice showed greater induction of zif 268 and homer 1, an effect that was most robust in the medial part of the mid-level striatum and became more pronounced with increasing age.
Conclusions: Together these findings indicate abnormally enhanced D-1 receptor signal transduction in adult mice after prenatal cocaine exposure. Such changes in dopamine receptor signaling might underlie aspects of long-lasting neuro-teratogenic effects evident in some humans after in utero exposure to cocaine and identify the striatum as one target potentially vulnerable to gestational cocaine exposure.

• 出版日期2008-6-1