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 (Ap(4)A) and diadenosine pentaphosphate (Ap(5)A) are costored with ATP and release d 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 wer e analyzed by HPLC. The adenine dinucleotides were not detectable befo re systemic amphetamine injection. The maximal levels were reached 20 min after injection, independently of the dose. The EC(50) values for amphetamine-induced release of dinucleotides were 2.04 +/- 0.15 and 2. 43 +/- 0.36 mg/kg for Ap(4)A and Ap(5)A, respectively. Amphetamine dos es 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 A p(4)A and Ap(5)A, respectively, which corresponds with 64.5 and 57.5 n M in the samples. Adenosine and AMP were present in push-pull samples from rat brain under basal conditions. Their levels were 15 pmol/fract ion (75 nM) and 50 pmol/fraction (250 nM) for adenosine and AMP, respe ctively. 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 A MP levels increased significantly from 10 to 50 min. The maximal level was reached 20 min after amphetamine injection, with 150 pmol/fractio n (750 nM), which represents a 200% increase with respect to the basal level. The adenine dinucleotide release was blocked by the dopamine r eceptor antagonist haloperidol, which returned the levels to the contr ol basal values. It is suggested that dopamine, released in a nonexocy totic way by the action of amphetamine, induces the release of the din ucleotides Ap(4)A and Ap(5)A in the neostriatum area through dopaminer gic receptors.