Chronic nicotine treatment eliminates asymmetry in striatal glucose utilization following unilateral transection of the mesostriatal dopamine pathway in rats.
Partial hemitransection was performed through a knife lesion at the meso-diencephalic level in rats to sever the mesostriatal dopamine system. During the subsequent 2 weeks the animals received 0.125 mg/kg/h of nicotine continuously via an osmotic minipump implanted s.c. To achieve prompt high nicotine levels, 4 i.p. injections of 0.5 mg/kg nicotine were, in addition, given during the first 2 h following the lesion. The total treatment corresponded to a mean plasma level of 50 ng/ml nicotine, measured at the end of the experiment. Control animals received corresponding volumes of 0.9% saline. Quantitative autoradiographic analysis of the glucose utilization in the caudate nucleus using Sokoloff's [14C]2-deoxyglucose method demonstrated a 16% side-to-side difference in the lesioned control animals, whereas the asymmetry was counteracted by the nicotine treatment. Although there was an overall tendency to a lower rate of glucose utilization (by 6%) in the nicotine-treated animals compared to the controls receiving saline only, the difference was not statistically significant. The eliminated asymmetry probably reflects an increased survival of the dopamine neurons and/or of striatal nerve cells on the lesioned side due to protective effects of nicotine resulting from desensitization of nicotinic-type cholinergic receptors following continuous administration of the drug.
Owman
C
C
Department of Medical Cell Research, University of Lund, Sweden.
Fuxe
K
K
Janson
A M
AM
Kåhrström
J
J
D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism; D002849:Chromatography, Gas; D003342:Corpus Striatum / Q000378:metabolism* / Q000601:surgery; D003367:Cotinine / Q000097:blood; D003714:Denervation; D003847:Deoxyglucose / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009538:Nicotine; D003847:Deoxyglucose; D005947:Glucose; D003367:Cotinine; D004298:Dopamine