Dopamine D1 and D2 receptor functional down regulation in the cerebellum of hypoxic neonatal rats: neuroprotective role of glucose and oxygen, epinephrine resuscitation

• Published in: Pharmacological research Vol. 61; no. 2; pp. 136 - 141
• Main Authors: Joseph, Binoy, Nandhu, M S, Paulose, C S
• Format: Journal Article
• Language: English
• Published: Netherlands 01-02-2010
• Subjects: Animals; Animals, Newborn; Benzamides - metabolism; Benzazepines - metabolism; Cerebellum - drug effects; Cerebellum - metabolism; Dopamine - metabolism; Dopamine Antagonists - metabolism; Down-Regulation; Epinephrine - administration & dosage; Glucose - administration & dosage; Homovanillic Acid - metabolism; Hypoxia, Brain - metabolism; Hypoxia, Brain - therapy; Neuroprotective Agents - administration & dosage; Oxygen Inhalation Therapy; Polymerase Chain Reaction; Protein Binding; Rats; Rats, Wistar; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism; Resuscitation - methods; RNA, Messenger - metabolism
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2009.08.007

Brain damage due to an episode of hypoxia remains a major problem in infants causing deficit in motor and sensory function. Molecular processes regulating the dopamine receptors play a very important role in motor and cognitive functions. Disturbances in the development of the dopaminergic system lead to dyskinesia, dystonia, tics and abnormal eye movements. The present study is to understand the hypoxic damage to the dopamine content and dopamine D(1), dopamine D(2) receptors in cerebellum and the neuroprotective effect of glucose supplementation prior to the current sequence of resuscitation-oxygen and epinephrine supplementation in neonatal rats. Dopamine content in the cerebellum showed a significant decrease in hypoxic neonatal rats when compared to control. Dopamine D(1) and dopamine D(2) receptors showed a decrease in B(max) during hypoxia. The cerebellar dopamine, dopamine D(1) and dopamine D(2) receptors showed significant decrease on supplementation of 100% oxygen alone to hypoxic rats when compared to control rats. Dopamine D(1) and dopamine D(2) receptors mRNA showed significant decrease during epinephrine supplementation prior to resuscitation. These dopaminergic receptor alterations were reversed to near control by glucose supplementation. Thus our results suggest that glucose acts as a neuroprotective agent in dopaminergic receptors function. This has immense clinical significance to correct the resuscitation sequence in neonatal care.