Reduction of voluntary alcohol consumption in the rat by transplantation of hypothalamic grafts

Abstract Stimulation of the peripheral renin-angiotensin system has been shown previously to decrease the voluntary intake of ethanol in the rat. The existence of a separate brain renin-angiotensin system, independent from that of the periphery, has been widely demonstrated. The brain renin-angiotensin system plays an important role in the regulation of water and electrolyte balance and neuroendocrine function. However, the role played by this system in the regulation of voluntary alcohol consumption has not yet been studied. The goal of the present work was to assess the feasibility of decreasing the voluntary alcohol intake in a strain of rats (Rapp SS/Jr rats) that have a genetic deficiency responsible for a low activity of the renin-angiotensin system and elevated alcohol intake. Adult Rapp SS/Jr rats received intraventricular transplants of fetal hypothalamic grafts (from normal donors), known to contain angiotensin-immunoreactive cell bodies. Our studies revealed that angiotensin-immunoreactivity in the cell bodies and fibres in the paraventricular, supraoptic and suprachiasmatic nuclei of the hypothalamus in Rapp SS/Jr rats was markedly reduced. Animals that had surviving grafts containing angiotensin-immunoreactive cell bodies in the dorsal third ventricle—but not in the ventral third ventricle, in the lateral ventricles, or sham operated animals—had a 40% decrease of their voluntary alcohol intake, when compared to their intake before surgery, or to the control group. However, water consumption was not reduced in both the sham and transplanted animals. The reduction of alcohol intake obtained after transplantation of angiotensin-producing cells suggests that the brain renin-angiotensin system may play a modulatory role in the regulation of voluntary alcohol intake, although they do not exclude the participation of other neurotransmitters in the modulation of alcohol consumption.