Involvement of the nerve flow in the release of extragranular dopamine

Autor: Erik L. Noach, Cees F.M. Van Valkenburg, Amerentia Wijling
Rok vydání: 1979
Předmět:
Zdroj: European Journal of Pharmacology. 57:191-199
ISSN: 0014-2999
DOI: 10.1016/0014-2999(79)90365-0
Popis: It is generally accepted that reserpine blocks the granular storage mechanism in catecholaminergic neurones and that (+)-amphetamine (AMP) releases dopamine (DA) from extragranular storage sites. In the present experiments it was investigated whether release from extragranular stores was dependent on ongoing nerve impulses. In three of the four experiments the accumulation of 3-methoxytyramine (3MT) after inhibition of monoamine oxidase was used as indicator for impulse-induced DA release. HA-966 (1-hydroxy-3-amino-pyrrolidone-2) or γ-hydroxybutyrate (GHB) was used to interrupt nerve impulses in the nigrostriatal pathway. After reserpine pre-treatment HA-966 and GHB blocked the pargyline-induced 3MT increase, while they increased DA levels concomitantly. If AMP was injected instead of reserpine, and no inhibitor of monoamine oxidase was given, no definite conclusion could be drawn about the interaction because AMP was suspected of partially inhibiting monoamine oxidase. Therefore monoamine oxidase was fully blocked by pargyline in two further experiments. Under these conditions HA-966 antagonized the AMP-induced 3MT accumulation, irrespective of whether a high (10 mg/kg) or a low (2 mg/kg) dose of AMP was given. GHB, however, was only effective if the low AMP dose was used. It is concluded that interruption of nerve impulses in the dopaminergic pathway inhibits the release from extragranular storage sites.
Databáze: OpenAIRE