Neurotensin studies in alcohol naive, preferring and non-preferring rats

Neurotensin is a tridecapeptide, present in the central nervous system and the gastrointestinal tract in man and animals. Previous studies in mice sel ectively bred for differences in hypnotic sensitivity to ethanol have provi ded data to suggest that neurotensinergic systems may mediate differences i n ethanol's actions in these animals. The present study sought to determine if brain neurotensin levels differed between two lines of rats which have been selectively bred for alcohol preferring or non-preferring behaviors. I n addition, electroencephalographic and event-related potential responses t o intracerebroventricular saline and neurotensin (10 or 30 mu g) were evalu ated between the rat lines. Similar to human subjects at high genetic risk for alcoholism, preferring rats were found to have more electroencephalogra phic fast frequency activity and lowered amplitude of the P3 component of t he event-related potential in cortical sites under the saline condition. Ov erall, electrophysiological response to neurotensin, in the two rats lines, was substantially similar to what has been reported previously in outbred Wistar rats, and consisted of dose-related decreases in overall electroence phalographic spectral power concomitant with increases in amplitude and dec reases in the latency of the N1 component of the event-related potential. H owever, differences in neurotensin responses between the preferring and non preferring rat lines were also found. The differences in electroencephalogr aphic high-frequency activity and in P3 amplitude seen between the rat line s under control conditions were eliminated by administration of neurotensin . In addition, preferring rats appeared to be more sensitive to neurotensin -induced increases in N1 amplitude. Brain neurotensin concentrations were a lso found to differ between the lines. Significantly lower concentrations o f neurotensin were found in the frontal cortex of preferring rats when comp ared to non-preferring rats or outbred Wistars. Taken together, these studies suggest that differences in the regulation of neurotensin neurons may contribute to the expression of behavioral prefere nce for ethanol consumption in selective rat lines. Additionally, drugs tar geting the neurotensinergic system may plausibly be of utility in the treat ment of alcoholism. (C) 1999 IBRO. Published by Elsevier Science Ltd.