Stimulated dopamine overflow and alpha-synuclein expression in the nucleus accumbens core distinguish rats bred for differential ethanol preference.
The key neurochemical systems and structures involved in the predisposition to substance abuse and preference to ethanol (EtOH) are not known in detail but clearly dopamine (DA) is an important modulator of addiction. Recent data indicate that alpha-synuclein (alpha-syn), a pre-synaptic protein, plays a role in regulation of DA release from the pre-synaptic terminals in striatum and the expression of this protein is different after drug abuse or following abstinence. In the present work, we analysed stimulated DA overflow in the dorsal and ventral striatum in EtOH naïve alko alchohol (AA) and alko non-alchohol (ANA) rats selected for more than 100 generations for their differential EtOH preference. In the same structures, we studied the expression of alpha-syn using western blotting. AA rats, in comparison with ANA rats, showed a marked reduction of stimulated peak DA overflow and higher levels of alpha-syn in the nucleus accumbens core. In the same structure, DA re-uptake was increased in AA rats in comparison with ANA rats. The effects of EtOH at low (0.1 g/kg) and higher (3 mg/kg) doses on DA overflow measured in the nucleus accumbens shell were similar in both lines. These results indicate that high expression of alpha-syn may contribute to the reduced DA overflow and the possible activation of re-uptake in the nucleus accumbens core of AA rats in comparison with ANA rats.
School of Pharmacy, University of Eastern Finland, Kuopio, Finland. anssi.pelkonen@uef.fi
Anssi
A
Pelkonen
Mikko
M
Hiltunen
Kalervo
K
Kiianmaa
Leonid
L
Yavich
D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012201:Reward; D013045:Species Specificity; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000235:genetics
D002492:Central Nervous System Depressants; D051844:alpha-Synuclein; D000431:Ethanol; D004298:Dopamine