P2 receptor-mediated effects on the open field behaviour of rats in comparison with behavioural responses induced by the stimulation of dopamine D2-like and by the blockade of ionotrophic glutamate receptors.
The effects of the P2 receptor ligands 2-methylthio ATP (2-MeSATP; 10 pmol)--as a non-specific agonist--and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10 pmol)--as a non-selective antagonist--after bilateral intra-accumbens injection on the locomotor response were investigated in an open field situation. The P2 receptor-mediated effects on the pattern of locomotor activity were compared with the effects caused by the dopamine D2-like receptor agonist quinpirole (10 pmol) and by the combination of the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 pmol) with the alpha-amino-3-hydro-5-methyl-4-isoxazolpropionic acid (AMPA) and kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 30 pmol). The intra-accumbens injection of all tested compounds elicited an increase in the locomotor activity over a test period of 20 min when compared with the controls. No statistically significant differences could be evaluated between the different drug-treated groups. However, a more detailed analysis--using further behavioural parameters such as the number of movement direction changes, the effective running time and the running speed--revealed two basically different patterns of locomotor activity. The locomotor response induced by the injection of 2-MeSATP or quinpirole was characterised by a continuous and consistent locomotion, whereas the enhanced locomotor activity elicited by PPADS or CPP/CNQX was determined by an increased running speed accompanied by more disruptions and more changes of movement direction. The coadministration of 2-MeSATP and quinpirole led to an enhancement of locomotor activity in a limited post-treatment interval. The effects of both compounds could be abolished by the pre-treatment with the D2/D3 receptor antagonist sulpiride (100 pmol). Coadministration of PPADS and CPP/CNQX caused additive effects suggesting that the pathway mediated by P2 and ionotrophic glutamate receptors is different. The stimulation of P2 receptors in the nucleus accumbens (NAc) modulates the locomotion in the direction to be to be longer lasting, more consistent and more goal directed.
Kittner
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Rudolf Boehm Department of Pharmacology and Toxicology, University of Leipzig, Härtelstrasse 16-18, D-04107 Leipzig, Germany. kith@medizin.uni-leipzig.de
Hoffmann
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Krügel
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Illes
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000255:Adenosine Triphosphate; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058910:Purinergic P2 Receptor Agonists; D011732:Pyridoxal Phosphate; D019257:Quinpirole; D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2; D017470:Receptors, Glutamate; D018048:Receptors, Purinergic P2; D013469:Sulpiride; D013873:Thionucleotides; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C008501:2-methylthio-ATP