The nicotinic receptor agonists (-)-nicotine and isoarecolone differ in their effects on dopamine release in the nucleus accumbens.
This study compared the effect of the nicotinic receptor agonists, (-)-nicotine and isoarecolone, on the mesolimbic dopamine system of the rat using in vivo microdialysis. Previous studies showed that (-)-nicotine but not isoarecolone produced a locomotor activating effect, and that this was probably mediated by increased concentrations of dopamine in the nucleus accumbens. Nicotine (0.4 mg/kg s.c.) significantly increased extracellular concentrations of dopamine and of dihydroxyphenylacetic acid (DOPAC) by 75-80% in nucleus accumbens of rats. Isoarecolone (3.2-32 mg/kg s.c.) had no significant effect on either dopamine or DOPAC levels in this brain region and neither drug affected extracellular levels of 5-hydroxy indole acetic acid. Both nicotine and isoarecolone induced head-bobbing behaviour. Pretreatment with ketanserin reduced nicotine-induced head-bobbing suggesting a serotonergic mechanism. In conclusion, the absence of locomotor activation after administration of isoarecolone may be related to its failure to activate the mesolimbic dopamine system.
Mirza
N R
NR
Institute of Psychiatry, Section of Behavioural Pharmacology, London, UK.
Pei
Q
Q
Stolerman
I P
IP
Zetterström
T S
TS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018722:Nicotinic Agonists; C095493:isoarecolone; D015102:3,4-Dihydroxyphenylacetic Acid; D001115:Arecoline; D009538:Nicotine; D004298:Dopamine