Potentiation of amphetamine-mediated responses in caffeine-sensitized rats involves modifications in A2A receptors and zif-268 mRNAs in striatal neurons.
Subchronic intermittent administration of caffeine induces sensitization of motor behaviour and promotes cross-sensitization to amphetamine motor activity. In order to evaluate the possible mechanisms at the basis of these effects, modifications in A(2A) receptor and zif-268 mRNAs were evaluated in rats subchronically treated with caffeine (15 mg/kg i.p.) and challenged with caffeine (15 mg/kg i.p.) or amphetamine (0.5, 1 mg/kg s.c.) 3 days after discontinuation of treatment. Results showed that the sensitized motor response to caffeine was associated with a decrease of adenosine A(2A) receptor and zif-268 mRNA levels in the striatum and nucleus accumbens, whereas cross-sensitization to amphetamine was linked to a more pronounced increase of zif-268 mRNA levels in the striatum, but not in the nucleus accumbens. Single-cell analysis showed that zif-268 mRNA modifications occurred in Enk(+) striatopallidal neurons after acute or subchronic treatment with caffeine and in Enk(-) striatonigral neurons after acute amphetamine administration. Potentiation of amphetamine effects was not associated with modifications of amphetamine-induced dopamine release in nucleus accumbens in caffeine-pretreated rats compared with vehicle-pretreated rats. Results demonstrate that sensitization to caffeine and cross-sensitization to amphetamine are associated with post-synaptic neuroadaptive changes in selective neuronal populations of the striatum.
Tronci
Elisabetta
E
Department of Toxicology, University of Cagliari, Cagliari, Italy.
Simola
Nicola
N
Carta
Anna R
AR
De Luca
M Antonietta
MA
Morelli
Micaela
M
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D017403:In Situ Hybridization; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis; D013569:Synapses / Q000378:metabolism
D000697:Central Nervous System Stimulants; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D002110:Caffeine; D000661:Amphetamine; D004298:Dopamine