Dopaminergic brain reward regions of Lewis and Fischer rats display different levels of tyrosine hydroxylase and other morphine- and cocaine-regulated phosphoproteins.
We studied cyclic AMP-dependent protein phosphorylation in the mesolimbic and nigrostriatal dopamine systems of two genetically inbred rat strains, Lewis (LEW) and Fischer (F344) rats. These strains represent genetically divergent populations of rats that have been used to study possible genetic factors involved in a variety of biological processes. We found striking differences in levels of tyrosine hydroxylase, and several other phosphoproteins, in the mesolimbic, but not the nigrostriatal, dopamine system between the two rat strains. Interestingly, in Sprague-Dawley rats, these same phosphoproteins are altered by chronic morphine and chronic cocaine specifically in the mesolimbic dopamine system, generally thought to be a brain reward pathway that mediates some of the reinforcing actions of many drugs of abuse. As LEW and F344 rats have been reported to show different levels of preference for several types of drugs of abuse, the results are consistent with the possibility that these phosphoproteins may mediate aspects of drug reinforcement and contribute to individual differences in vulnerability to drug addiction.
Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven 06508.
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Beitner-Johnson
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Guitart
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Nestler
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D005838:Genotype; D009020:Morphine / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012201:Reward; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects* / Q000378:metabolism
D010750:Phosphoproteins; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D004298:Dopamine