Implication of Cerebral Dopamine-β Hydroxylase for Cardiovascular and Mood Regulation in Rats

Abstract

The essentiality of the role of norepinephrine (NE) in the central nervous system has recently been reconsidered. NE exerts many effects and mediates a number of functions in living organisms. Dopamine-beta-hydroxylase (DBH) is the crucial enzyme for NE and epinephrine biosynthesis. Removal of this enzyme causes deficient NE at sympathetic terminals characterized by orthostatic hypotension in humans. The hypothesis tested in this study was that NE deficiency in the central nervous system caused autonomic failure in cardiovascular regulation. The immunotoxin anti-DBH-saporin (DSAP) was used to examine the putative role of cerebral NE. Male Sprague-Dawley rats were injected, intracerebroventricularly (icv), with DSAP and cardiovascular reactivity, as well as behavioral variables in the open-field locomotion test (OLT), sucrose intake test (SIT) and forced swim test (FST), were monitored for changes. The results indicated that treatment with DSAP caused significant reductions in spontaneous blood pressure (BP) and heart rate (HR), and a decrease in the rearing position on the OLT, in the same group of rats. In addition, a significant increase in mobility with low concurrent immobility frequencies was observed on the FST. However, there was no variation on the SIT. In conclusion, a deficiency in the cerebral DBH might dysregulate the autonomic outflows and, thus, leads to lower BP and HR. However, there was no mood change such as despair or anhedonia observed in the experiments.