Effect of acute nicotine on Fos protein expression in rat brain during chronic nicotine and its withdrawal.
To study the cholinergic regulation of hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei and interpeduncular nucleus (IPN) we investigated the effects of acute nicotine (0.5 mg/kg, SC, 60 min) on Fos-like immunostaining (IS) during chronic nicotine and its withdrawal in rats. Nicotine or saline was infused to rats via osmotic minipumps (4 mg/kg/day) for 7 days; on the seventh day, the minipumps were removed surgically. In control rats, acute nicotine increased Fos IS significantly in all three brain areas studied. On the seventh day of nicotine infusion this effect partially persisted in IPN but was abolished in PVN and SON. After 72-h withdrawal nicotine-induced elevation of Fos IS was similar to that of control rats in all three areas. The observed attenuation of the response to acute nicotine during constant nicotine infusion in PVN and SON may be attributable to the desensitization of nicotinic acetylcholine receptors (nAChRs) mediating the effects of nicotine in these areas or in their input areas. IPN is connected to midbrain limbic system, so in agreement with our earlier observations, it seems that limbic nicotinic receptors do not very readily desensitize during chronic nicotine infusion. These findings support the suggestions that there are differences in the level of desensitization of nAChRs.
Salminen
O
O
Division of Pharmacology & Toxicology, Department of Pharmacy, P.O. Box 56, FIN-00014 University of Helsinki, Finland.
Seppä
T
T
Gäddnäs
H
H
Ahtee
L
L
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000633:toxicity*; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000737:chemistry / Q000187:drug effects
D016760:Proto-Oncogene Proteins c-fos; D011978:Receptors, Nicotinic; D009538:Nicotine; D000324:Adrenocorticotropic Hormone