Chronic nicotine treatment increases dopamine levels and reduces dopamine utilization in substantia nigra and in surviving forebrain dopamine nerve terminal systems after a partial di-mesencephalic hemitransection.
In order to further study the previously demonstrated protective action of chronic nicotine treatment on lesioned meso-striatal dopamine (DA) pathways, the following study was carried out on DA utilization in these lesioned neurons. Male Sprague-Dawley rats were partially hemitransected at the meso-diencephalic junction and treated with nicotine (0.125 mg.kg-1.h-1) by means of Alzet minipumps implanted subcutaneously for 2 weeks. The overall serum nicotine level obtained was 64.6 +/- 2.7 ng.ml-1. The results demonstrated that partial di-mesencephalic hemitransections produced a marked reduction of DA fluorescence (quantitative histofluorimetry) on the lesioned side in the nucleus caudatus putamen, anterior nucleus accumbens and posterior lateral tuberculum olfactorium. No significant effects were observed on the intact side. Furthermore, studies on changes in DA utilization as evaluated 2 h after tyrosine hydroxylase inhibition showed an augmentation in the alpha-methyl-(+/-)-p-tyrosine methyl ester (alpha-MT)-induced depletion of the DA stores on the hemitransected side in comparison with the operated side of the sham-operated animals. On the hemitransected side chronic nicotine treatment increased DA stores in the DA nerve terminals of the nucleus caudatus putamen and the posterior lateral tuberculum olfactorium. No significant effects were observed on the intact side. Following chronic nicotine treatment a marked and preferential attenuation of the alpha-MT-induced depletion of DA stores was seen in the various DA nerve terminal systems of the forebrain on the hemitransected side. In the substantia nigra reduced DA levels (HPLC) were demonstrated on the hemitransected side, while no effects on the non-operated side were observed. Also an increase of the alpha-MT-induced depletion of the DA stores was seen on the hemitransected side in comparison with the operated side of the sham-operated animals. In contrast, on the non-operated side an attenuation of the alpha-MT-induced depletion of the DA stores was found. Following chronic nicotine treatment the lesion induced reduction of the nigral DA stores on the hemitransected side was counteracted, as was the lesion induced increase in the alpha-MT-induced depletion of DA stores, which was replaced by a reduction of the alpha-MT-induced depletion of the nigral DA stores. However, on the non-operated side an increased DA depletion was observed after alpha-MT treatment in rats treated chronically with nicotine. Chronic nicotine treatment under the present conditions did not significantly alter serum levels of corticosterone and reduced prolactin serum levels in sham-operated rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Fuxe
K
K
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Janson
A M
AM
Jansson
A
A
Andersson
K
K
Eneroth
P
P
Agnati
L F
LF
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood; D003367:Cotinine / Q000097:blood; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D008297:Male; D008636:Mesencephalon / Q000502:physiology*; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D002395:Catecholamines; D009538:Nicotine; D011388:Prolactin; D003367:Cotinine; D004298:Dopamine; D003345:Corticosterone