NEUROTENSIN LEVELS AND RECEPTORS IN HAS AND LAS RAT BRAINS - EFFECTS OF ETHANOL

Previous studies of neurotensin (NT) levels and NT receptor densities in specific brain regions of mice selectively bred for differences in sensitivity to ethanol have shown that NTergic processes may mediate s ome actions of ethanol. In the present study, we have determined the l evels of NT and NT receptor densities in specific brain regions of HAS and LAS rats that have been selectively bred for differences in sensi tivity to ethanol-induced loss of righting response. Regional differen ces in NT levels were observed in brains from both HAS and LAS rats an d values in hypothalamus, ventral midbrain, and nucleus accumbens from female rats were 25 to 75% higher than levels in corresponding region s from male rats. However, there were no significant line differences in NT-ir levels in corresponding regions from HAS and LAS animals. Hig h-affinity binding (NTH B-max values), measured by Scatchard analyses, were higher in ventral midbrain from HAS males than from LAS males. N TH receptor densities were higher in HAS males than in HAS females; se x differences were not observed in the LAS line. There were no signifi cant line or sex differences between HAS and LAS in low-affinity (NTL) B-max values in any brain region. In HAS females, subhypnotic doses o f ethanol produced a decrease in NT levels in nucleus accumbens, where as, hypnotic doses caused an increase in NT levels. Likewise, hypnotic doses elicited increases in NT levels in hypothalamus of female HAS a nd LAS, but not in ventral midbrain or caudate putamen. These results are consistent with low dose activation of mesolimbic and nigrostriata l dopaminergic neurons in which NT is colocalized with dopamine and wi th high dose inhibition of these pathways.