Effects of intra-accumbens injection of 2-methylthio ATP: a combined open field and electroencephalographic study in rats.
BACKGROUND
Previous experiments have shown that P2 receptor activation increases the release of dopamine in the mesolimbic mesocortical system.


OBJECTIVE
In order to investigate the functional correlates of dopaminergic stimulation, EEG and behavioural responses to injection of the P2 receptor agonist 2-methylthio ATP (2-MeSATP) into the nucleus accumbens (NAc) of rats were investigated.


METHODS
EEG electrodes were positioned into the NAc together with the guide cannula for intracerebral injection. Behavioural analysis was performed in an open field cage and was evaluated by a video activity measurement system. Rats were assigned to separate groups that were given artificial cerebrospinal fluid (aCSF) or drug treatment.


RESULTS
2-MeSATP significantly extended the period of locomotor activity in the novel environment. The quantitative EEG was characterized by an elevation of the power in the alpha-range and a decrease in power in the delta range. The P2 receptor antagonists reactive blue 2 but not pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid (PPADS) also enhanced locomotion when given alone, and elevated the alpha-1 and beta-2 bands. Both antagonists abolished the locomotor and EEG responses to 2-MeSATP. The dopamine D1 receptor antagonist SCH 23390 and the D2/D3 receptor antagonist sulpiride did not alter locomotor activity when given either alone or in combination. Only sulpiride and especially sulpiride in combination with SCH 23390 prevented the effect of 2-MeSATP. Sulpiride produced a selective increase in the alpha-1 band of the power spectrum whereas SCH 23390 elevated the power of the alpha-1, alpha-2 and beta-1 activities. Neither antagonist inhibited the effect of 2-MeSATP on the EEG when applied separately; however, the co-administration of SCH 23390 and sulpiride abolished the 2-MeSATP-induced alteration of power distribution. After a 6-hydroxydopamine (6-OHDA)-induced lesion of the accumbal dopaminergic terminals, 2-MeSATP failed to enhance the locomotor activity and to induce the characteristic EEG changes.


CONCLUSIONS
The observed alterations in open field behaviour and quantitative EEG after injection of 2-MeSATP into the NAc may be mostly due to P2 receptor-mediated dopamine release and subsequent receptor activation.
Kittner
H
H
Department of Pharmacology, University of Leipzig, Germany.
Krügel
U
U
Hoffmann
E
E
Illes
P
P
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D018663:Adrenergic Agents; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology*
D018663:Adrenergic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D016627:Oxidopamine; D000255:Adenosine Triphosphate; C008501:2-methylthio-ATP