Effect of nicotine and cocaine on neurofilaments and receptors in whole brain tissue and synaptoneurosome preparations.
The present study examined the effect of repeated nicotine and cocaine administration on the expression of neurofilament proteins (NF-L, -M, and -H), actin, and on alpha-7 nicotinic, dopamine D1 and NMDA NR1 receptors in brain. Whole tissue homogenate and synaptoneurosomal preparations from hippocampus, striatum and cortex were assayed. C57BL/6By mice were treated for 2 weeks with a daily injection of nicotine (0.4 mg/kg) or cocaine (25mg/kg). The mice were killed 60 min after the last injection and tissue prepared for Western blot analysis of expression of NFs and receptor expression. Actin protein was affected by cocaine and nicotine treatment, decreasing in homogenate fraction (striatum and cortex) and showing an increase in the synaptoneurosome preparation (hippocampus and cortex). NF expression was affected; with regional and response differences dependent on tissue preparation. NF-M increased in all three brain regions; NF-L increased in the cortex and NF-H increased in the striatum in the synaptoneurosomal preparations. Change in nicotinic and dopamine receptor expression was dependent on region and tissue preparation. NMDA NR1 expression increased in the three brain regions in the synaptoneurosomal preparation. The results suggest that specific brain protein levels are affected by repeated drug administration. Drug effects on cytoskeletal elements are selective, regionally heterogeneous, and change with time after drug administration. Changes in cytoskeletal proteins maybe part of the mechanism in drug-induced neurotransmitter changes. We have found previously that drug-induced changes in neurotransmitters are regionally heterogeneous and are drug specific. We now found similar regional heterogeneity and drug specificity in drug-induced changes in cytoskeletal and receptor proteins.
Kovacs
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K
Nathan S. Kline Institute, 140 Old Orangeburg Rd., Orangeburg, NY 10962, United States.
Lajtha
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A
Sershen
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H
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D018765:Dopamine Uptake Inhibitors; D005731:Ganglionic Stimulants; D007381:Intermediate Filament Proteins; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D003042:Cocaine