Modification of inherent and drug-induced dopaminergic activity after exposure to benzo(alpha)pyrene.
The aim of this study was to investigate the effect of benzo(alpha)pyrene (B(alpha)P), a representative polycyclic aromatic hydrocarbon (PAH), on dopaminergic activity in brain. (B(alpha)P) altered dopaminergic activity in discrete regions of the rat brain, including the hippocampus, hypothalamus, caudate putamen and nucleus accumbens. Specifically, B(alpha)P increased DA levels in the hippocampus and DA turnover in the caudate putamen. In addition, B(alpha)P suppressed DA levels in the caudate putamen and DA turnover in the nucleus accumbens. B(alpha)P also altered the effect of several dopaminergic agents, L-DOPA, sulpiride and bromocriptine, on DA activity. In particular, B(alpha)P enhanced the L-DOPA-induced increase in the DA turnover ratio in the caudate putamen and increased DA levels in the nucleus accumbens. B(alpha)P also reversed the sulpiride-induced increase of DA turnover in the nucleus accumbens and the bromocriptine-induced increase of DA turnover in the hippocampus. In addition, DA turnover was increased by B(alpha)P in the nucleus accumbens and caudate putamen and DA levels were suppressed in the nucleus accumbens of bromocriptine treated rats, though the drug alone had no effect. These changes indicate that exposure to B(alpha)P and related compounds may affect dopaminergic function in discrete brain regions that are implicated in cognitive functions, psychosis, depression and Parkinson's disease, and may possibly interfere with their pharmacological intervention.
Konstandi
Maria
M
Department of Pharmacology, School of Medicine, University of Ioannina, Ioannina, Greece. mkonstan@cc.uoi.gr
Harkitis
Panagiotis
P
Thermos
Kyriaki
K
Ogren
Sven Ove
SO
Johnson
Elizabeth O
EO
Tzimas
Panagiotis
P
Marselos
Marios
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D001971:Bromocriptine / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage*; D004347:Drug Interactions; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000008:administration & dosage
D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D001564:Benzo(a)pyrene; D001971:Bromocriptine; D013469:Sulpiride; D004298:Dopamine; D006719:Homovanillic Acid