Corticosterone urinalysis and nicotinic receptor modulation in rats.
A routine method of measuring circulating corticosterone (CORT) levels in rats involves sampling of plasma from cannulated animals. However, being somewhat invasive, this method can potentially be confounded by its inherently stressful nature. This study investigated the feasibility of measuring corticosterone using a non-invasive sampling method from voided urine of male rats. Reliability was assessed pharmacologically with nicotinic compounds previously demonstrated to modulate plasma glucocorticoid levels. Nicotine (0.1-1mg/kg sc) dose-dependently increased corticosterone levels in rat urine at 30-70 min following administration. The short-lived nature of this elevation was confirmed as CORT levels measured 6 and 24h later were shown to have returned to basal levels. Both basal and nicotine-induced (0.5mg/kg sc) elevations in urinary CORT were consistent between groups of animals with weights ranging from 200 to 400 g. The magnitude of urinary CORT elevation induced by nicotine (0.5mg/kg sc) was found to be similar to that induced by a forced swim stressor in male Lister ) antagonist mecamylamine (0.05-0.5mg/kg sc) dose-dependently reversed the effects of nicotine (0.5mg/kg sc) on urinary CORT. Finally, the alpha(4)beta(2)-subunit preferring agonist TC-2559 induced a dose-dependent increase in CORT, whereas alpha(7)- and beta(4)-subunit preferring ligands had no effect, suggestive of the potential for differential involvement of nicotinic receptor subtypes in the mediation of this response. In conclusion, urinary corticosterone sampling in rats represents a robust assay sensitive to experimental manipulations of both pharmacological and behavioural relevances.
Loomis
Sally
S
Eli Lilly & Co. Ltd, Psychiatric Disorders Drug Hunting Team, Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, UK.
Gilmour
Gary
G
D000818:Animals; D001681:Biological Assay / Q000379:methods; D003345:Corticosterone / Q000032:analysis* / Q000097:blood / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009480:Neuropharmacology / Q000379:methods*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D016482:Urinalysis / Q000379:methods*
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C419442:TC 2559; C403531:nicotinic receptor alpha4beta2; D008464:Mecamylamine; D009538:Nicotine; D003345:Corticosterone