Alcohol‐Preferring and Nonpreferring Rats Display Different Levels of Neurofilament Proteins in the Ventral Tegmental Area

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Abstract
Previously, different levels of neurofilaments (NF) in the ventral tegmental area (VTA) have been identified in Sprague-Dawley rats treated chronically with morphine or cocaine and in drug-naive Lewis and Fischer 344, inbred strains that differ behaviorally in several ways, including alcohol, opiate, and cocaine preferences. These findings led us to examine whether rat lines that have been selectively bred for a difference in alcohol preference, the alcohol-preferring (P) and nonpreferring (NP) rats, also express different levels of NFs in the VTA. We found by use of back phosphorylation and immunolabeling procedures that the VTA of the P rat contains 20-50% lower levels of the three major types of NF proteins--NF-200, NF-160, and NF-68--compared with the VTA of the NP rat. No strain difference in NF levels was seen in the substantia nigra (which like the VTA is a major dopaminergic nucleus in brain), locus coeruleus (which is a major noradrenergic nucleus in brain), or spinal cord (which is enriched in NF proteins). In contrast to NFs, no P-NP line differences were found in VTA levels of tyrosine hydroxylase, which is also regulated by chronic morphine and cocaine treatments in Sprague-Dawley rats and shows prominent Lewis-Fischer strain differences, specifically in this brain region. The results provide additional support for the possibility that levels of NFs in the VTA may be related to preference for alcohol and other drugs of abuse.