Individual differences in locomotor activity are associated with levels of tyrosine hydroxylase and neurofilament proteins in the ventral tegmental area of sprague-dawley rats.
We have demonstrated previously that chronic morphine and cocaine treatments increase levels of tyrosine hydroxylase (TH), and decrease levels of neurofilament (NF) proteins, in the ventral tegmental area (VTA), a major dopaminergic brain reward region, of outbred Sprague-Dawley rats. We have also found inherent differences in levels of these proteins in the VTA of inbred rat strains that differ in their behavioral responses to opiates, cocaine, and other drugs of abuse, with the Lewis rat showing higher levels of TH and lower levels of NFs in the VTA compared to the Fischer 344 rat. Based on recent reports that individual differences in drug responses among outbred Sprague-Dawley rats are highly correlated with the animals' locomotor response to novelty, we determined in the present study whether such within-strain differences in locomotor behavior are also associated with differences in levels of TH and NFs in the VTA. Groups of 42 Sprague-Dawley rats were assessed for locomotor activity in a novel environment. The four animals from each group with the lowest locomotor responses (designated L rats), and the four with the highest locomotor responses (designated H rats), were analyzed for TH and NF immunoreactivity by immunoblotting procedures. It was found that the VTA of L rats exhibited higher levels of TH and lower levels of three major NF proteins, NF-200, NF-160, and NF-68, compared to the VTA of H rats. A tendency for similar L versus H differences in TH and NF levels were observed when groups of rats with the second lowest and second highest locomotor responses were compared; no differences were seen in groups whose locomotor responses were closer to the median. These biochemical differences between H and L rats showed regional specificity, with no significant differences seen in several other regions of brain or spinal cord studied. Differences were also observed between L and H rats in their locomotor responses to acute and repeated cocaine exposure. The possible relationship between the individual differences in TH and NFs and individual differences in locomotor activity and other drug-related behaviors is discussed.
Miserendino
M J
MJ
Laboratory of Molecular Psychiatry, Departments of psychiatry and Pharmacology, Yale University School of Medicine and Connecticut Mental Health Center, 34 Park Street New Haven, Connecticut 06508.
Guitart
X
X
Terwilliger
R Z
RZ
Chi
S
S
Nestler
E J
EJ