Enhanced P2Y1 receptor expression in the brain after sensitisation with d-amphetamine.
OBJECTIVE
Many pathological and physiological processes are associated with the transcriptional induction of specific receptors. The aim of the present study was to examine whether the development of d-amphetamine (AMPH)-induced sensitisation is related to an altered P2Y(1) receptor expression.


METHODS
Rats, treated for 5 successive days with AMPH (1.5 mg/kg, i.p.), alone or after pre-treatment with the non-specific P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2,4-disulphonic acid (PPADS, 0.6 nmol, i.c.v.) and tested in an open field system with respect to locomotor response, were studied immunocytochemically 5 days after the last AMPH injection.


RESULTS
In the behaviourally sensitised animals, astrogliosis, characterised by hypertrophy, increase in glial fibrillary acidic protein (GFAP) immunoreactivity (IR) and astrocytic proliferation in striatal areas and the nucleus accumbens were observed. Quantification of the P2Y(1) receptor stained cells revealed an increase in the receptor expression after AMPH-induced sensitisation in the studied regions. Pre-treatment with PPADS prior to each AMPH administration prevented the development of sensitisation, astrogliosis and P2Y(1) receptor up-regulation. PPADS failed to alter the number of P2Y(1) receptor-labelled cells when given alone. Confocal laser scanning microscopy indicated the localisation of P2Y(1) receptors on GFAP-labelled astrocytes as well as on tubulin (betaIII)-labelled neurones, under control conditions and after AMPH administration.


CONCLUSIONS
The present results confirm the existence of P2Y(1) receptors on astrocytes and neurones as possible targets of endogenous ATP and in addition show their up-regulation as a consequence of P2Y(1) receptor-involvement in AMPH-induced sensitisation in vivo.
Franke
Heike
H
Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Härtelstrasse 16-18, 04107 Leipzig, Germany. frah@medizin.uni-leipzig.de
Kittner
Holger
H
Grosche
Jens
J
Illes
Peter
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D014404:Tubulin / Q000378:metabolism
D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D014404:Tubulin; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D003913:Dextroamphetamine