Effect of acute administration of nicotine on in vivo release of noradrenaline in the hippocampus of freely moving rats: a dose-response and antagonist study.
The effect of systemic administration of (-)-nicotine on release of noradrenaline in the hippocampus was studied by in vivo microdialysis in freely moving rats, using dialysate containing nomifensine (5 microM). (-)-Nicotine, at both 0.4 and 0.8 mg/kg but not 0.2 mg/kg, rapidly and significantly increased extracellular levels of noradrenaline. Extracellular levels of dopamine were also increased, but this was only significant after the larger dose. Both 0.4 and 0.8 mg/kg also produced a significant increase in extracellular levels of the metabolites of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid. Extracellular levels of the metabolite of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, increased after 0.8 mg/kg but this effect was only apparent much later. Injection of a second 0.8 mg/kg challenge of (-)-nicotine, 150 min after the first, produced similar increases in extracellular levels of noradrenaline, dopamine, 3-4-dihydroxyphenylacetic acid and homovanillic acid. Over the experimental period, there was no further increase in extracellular levels of 5-hydroxyindoleacetic acid. Increases in extracellular levels of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in response to 0.8 mg/kg (-)-nicotine, were prevented by the systemic administration of mecamylamine, but not hexamethonium (both at 5 mg/kg). Mecamylamine also inhibited the delayed increase in extracellular levels of 5-hydroxyindoleacetic acid, produced by the first injection of (-)-nicotine. These results suggest that (-)-nicotine, dose-dependently stimulated the release and metabolism of amine transmitters by an action at central nicotinic receptors. However, the precise site of action, i.e. at nerve terminals, cell bodies or both, requires further elucidation.
Department of Psychology, Institute of Psychiatry, Denmark Hill, London, U.K.
M P
MP
Brazell
S N
SN
Mitchell
J A
JA
Gray
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006584:Hexamethonium Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid