Dopamine Receptor Blockade Inhibits the Amphetamine‐Induced Release of Diadenosine Polyphosphates, Diadenosine Tetraphosphate and Diadenosine Pentaphosphate, from Neostriatum of the Conscious Rat
The diadenosine polyphosphates diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) are costored with ATP and released in a calcium-dependent manner from neural preparations in vitro. By means of a push-pull perfusion system, samples from conscious rat were collected from the caudate putamen area, and nucleotide compounds were analyzed by HPLC. The adenine dinucleotides were not detectable before systemic amphetamine injection. The maximal levels were reached 20 min after injection, independently of the dose. The EC50 values for amphetamine-induced release of dinucleotides were 2.04 ± 0.15 and 2.43 ± 0.36 mg/kg for Ap4A and Ap5A, respectively. Amphetamine doses higher than 5 mg/kg did not increase the dinucleotide release, the maximal values being 12.9 ± 0.9 and 11.5 ± 0.9 pmol/fraction for Ap4A and Ap5A, respectively, which corresponds with 64.5 and 57.5 nM in the samples. Adenosine and AMP were present in push-pull samples from rat brain under basal conditions. Their levels were 15 pmol/fraction (75 nM) and 50 pmol/fraction (250 nM) for adenosine and AMP, respectively. A significant increase was obtained for both compounds after amphetamine injection. The adenosine increase reached 45 pmol/sample (225 nM), which was 200% of the basal value 20 min after the stimulant administration. The increase at other times was not significant. The AMP levels increased significantly from 10 to 50 min. The maximal level was reached 20 min after amphetamine injection, with 150 pmol/fraction (750 nM), which represents a 200% increase with respect to the basal level. The adenine dinucleotide release was blocked by the dopamine receptor antagonist haloperidol, which returned the levels to the control basal values. It is suggested that dopamine, released in a nonexocytotic way by the action of amphetamine, induces the release of the dinucleotides Ap4A and Ap5A in the neostriatum area through dopaminergic receptors.