Chronic nicotine modifies the effects of morphine on extracellular striatal dopamine and ventral tegmental GABA.
Previously, we have shown that 7-week oral nicotine treatment enhances morphine-induced behaviors and dopaminergic activity in the mouse brain. In this study, we further characterized the nicotine-morphine interaction in the mesolimbic and nigrostriatal dopaminergic systems, as well as in the GABAergic control of these systems. In nicotine-pretreated mice, morphine-induced dopamine release in the caudate putamen and nucleus accumbens was significantly augmented, as measured by microdialysis. Chronic nicotine treatment did not change basal extracellular concentrations of dopamine and its metabolites in the caudate putamen and nucleus accumbens, nor did it affect the rate of dopamine synthesis, as assessed by 3-hydroxybenzylhydrazine dihydrochloride-induced DOPA accumulation. GABAergic control of dopaminergic activity was studied by measuring extracellular GABA in the presence of nipecotic acid, an inhibitor of GABA uptake. Acute (0.3 mg/kg or 0.5 mg/kg i.p.) and chronic nicotine, as well as morphine (15 mg/kg s.c.) in control mice decreased nipecotic acid-induced increase in extracellular GABA in the ventral tegmental area/substantia nigra (VTA/SN). In contrast, in nicotine-treated mice, morphine increased GABA levels in the presence of nipecotic acid. We did not find any alterations in GABA(B)-receptor function after chronic nicotine treatment. Thus, our data show that chronic nicotine treatment sensitizes dopaminergic systems to morphine and affects GABAergic systems in the VTA/SN.
Vihavainen
Tanja
T
Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. tanja.vihavainen@helsinki.fi
Relander
Toni R A
TR
Leiviskä
Riikka
R
Airavaara
Mikko
M
Tuominen
Raimo K
RK
Ahtee
Liisa
L
Piepponen
Timo Petteri
TP
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D013995:Time; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D009294:Narcotics; D018377:Neurotransmitter Agents; D018722:Nicotinic Agonists; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D004295:Dihydroxyphenylalanine; D009538:Nicotine; D009020:Morphine; D004298:Dopamine; D006719:Homovanillic Acid