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 some actions of ethanol. In the present study, we have determined the levels of NT and NT receptor densities in specific brain regions of HAS and LAS rats that have been selectively bred for differences in sensitivity to ethanol-induced loss of righting response. Regional differences in NT levels were observed in brains from both HAS and LAS rats and values in hypothalamus, ventral midbrain, and nucleus accumbens from female rats were 25 to 75% higher than levels in corresponding regions from male rats. However, there were no significant line differences in NT-ir levels in corresponding regions from HAS and LAS animals. High-affinity binding (NTH Bmax values), measured by Scatchard analyses, were higher in ventral midbrain from HAS males than from LAS males. NTH receptor densities were higher in HAS males than in HAS females; sex differences were not observed in the LAS line. There were no significant line or sex differences between HAS and LAS in low-affinity (NTL) Bmax values in any brain region. In HAS females, subhypnotic doses of ethanol produced a decrease in NT levels in nucleus accumbens, whereas, hypnotic doses caused an increase in NT levels. Likewise, hypnotic doses elicited increases in NT levels in hypothalamus of female HAS and LAS, but not in ventral midbrain or caudate putamen. These results are consistent with low dose activation of mesolimbic and nigrostriatal dopaminergic neurons in which NT is colocalized with dopamine and with high dose inhibition of these pathways.
Erwin
V G
VG
Alcohol Research Center, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Draski
L J
LJ
Deitrich
R A
RA
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006234:Handling, Psychological; D007700:Kinetics; D008297:Male; D009496:Neurotensin / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D018028:Receptors, Neurotensin / Q000378:metabolism*; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000523:psychology
D002492:Central Nervous System Depressants; D018028:Receptors, Neurotensin; D009496:Neurotensin; D000431:Ethanol