Effects of intra-accumbens injection of 2-methylthio ATP:: a combined open field and electroencephalographic study in rats

Rationale: Previous experiments have shown that P-2 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 P-2 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-1 range and a decrease in power in the delta range. The P2 receptor antagonists reactive blue 2 but not pyridoxal-phosphate-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 D-1 receptor antagonist SCH 23390 and the D-2/D-3 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 '3390 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 coadministration 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 P-2 receptor-mediated dopamine release and subsequent receptor activation.