Potentiation of amphetamine-mediated responses in caffeine-sensitized rats involves modifications in A2A receptors and zif-268 mRNAs in striatal neurons.

Full Abstract

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.

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Author information

Author/s: Tronci, Elisabetta (E); Simola, Nicola (N); Carta, Anna R (AR); De Luca, M Antonietta (MA); Morelli, Micaela (M);

Affiliation: Department of Toxicology, University of Cagliari, Cagliari, Italy.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of neurochemistry (J Neurochem), published in England. (Language: eng)

Reference: 2006-Aug; vol 98 (issue 4) : pp 1078-89

Dates: Created 2006/08/09; Completed 2006/09/21; Revised 2006/11/15;

PMID: 16771831, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amphetamine - pharmacology
Animals
Autoradiography
Caffeine - pharmacology
Central Nervous System Stimulants - pharmacology
Dopamine - metabolism
Drug Synergism
In Situ Hybridization
Male
Microdialysis

Motor Activity - drug effects
Neostriatum - cytology; drug effects; metabolism
Neurons - drug effects; metabolism
Nucleus Accumbens - metabolism
RNA, Messenger - biosynthesis
Rats
Rats, Sprague-Dawley
Receptor, Adenosine A2A - drug effects
Receptors, Dopamine D2 - biosynthesis
Synapses - metabolism

Associated Chemicals: Central Nervous System Stimulants (0) ; RNA, Messenger (0) ; Receptor, Adenosine A2A (0) ; Receptors, Dopamine D2 (0) ; Amphetamine (300-62-9) ; Dopamine (51-61-6) ; Caffeine (58-08-2)

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