Further studies on the stimulatory action of nicotine on adrenocortical function in the rat.
The aim of the present study was to further characterize the site of action of nicotine-induced hypothalamo-hypophyseal-adrenal (HHA) activation. A systemic injection of nicotine in concentrations of 65-2,100 micrograms/kg elevated serum corticosterone (CS) concentrations in a time and dose-dependent manner. Serum ACTH levels were also significantly increased. Pretreatment with dexamethasone (40 micrograms/kg) or the nicotinic antagonist, mecamylamine (1 mg/kg), abolished the ACTH and CS secretory responses to nicotine. Intracerebroventricular administration of antinicotinic acetylcholine receptor antibodies, prepared from the serum of myasthenia gravis patients, completely inhibited the nicotine-induced HHA activation. Bilateral lesions of the paraventricular nucleus similarly inhibited the nicotine-induced adrenocortical activity. These results suggest that nicotine activates the HHA axis by a central mechanism which ultimately requires the integrity of the paraventricular nucleus. Moreover, these findings indicate that the nicotinic adrenocortical effect is mediated specifically through activation of central nicotinic cholinergic receptors.
Weidenfeld
J
J
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Bodoff
M
M
Saphier
D
D
Brenner
T
T
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology / Q000601:surgery; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology; D013997:Time Factors
D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone