Ethanol, like psychostimulants and morphine, causes long-lasting hyperreactivity of dopamine and acetylcholine neurons of rat nucleus accumbens: possible role in behavioural sensitization.
Repeated treatment of rats with ethanol (1 g/kg, once daily for 15 days) enhanced the locomotor effect of morphine, 3 weeks post-treatment. This ethanol-induced long-term behavioural sensitization to morphine was associated with an increase in the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) from nucleus accumbens slices. A similar enhanced responsiveness of accumbal dopaminergic and cholinergic neurons to depolarization was apparent 3 weeks after repeated morphine, amphetamine or cocaine administration. Prior ethanol exposure also caused a long-term enhancement of electrically evoked release of [3H]DA and [14C]ACh from slices of the caudate-putamen. Unlike the locomotor effect of morphine, that of amphetamine was not enhanced in ethanol-pretreated rats. These data indicate that ethanol administration may cause long-term behavioural sensitization associated with adaptive changes in dopaminergic and cholinergic neurons of rat nucleus accumbens and caudate-putamen. Furthermore, an enhanced reactivity of nucleus accumbens dopaminergic nerve terminals and dopamine-sensitive cholinergic neurons appears to be a common long-term neuroadaptive effect of distinct types of addictive drugs. However, since repeated ethanol exposure did not cause a long-term increase in the locomotor effect of amphetamine, these neuroadaptations may not always be sufficient to cause long-lasting behavioural (cross-)sensitization.
Nestby
P
P
Research Institute Neurosciences Vrije Universiteit, Faculty of Medicine, Department of Pharmacology, Free University, Amsterdam, The Netherlands.
Vanderschuren
L J
LJ
De Vries
T J
TJ
Hogenboom
F
F
Wardeh
G
G
Mulder
A H
AH
Schoffelmeer
A N
AN
D000109:Acetylcholine / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D009294:Narcotics; D000431:Ethanol; D009020:Morphine; D000661:Amphetamine; D003042:Cocaine; D000109:Acetylcholine; D004298:Dopamine