Characterization of acute intrastriatal effects of paraoxon on in vivo dopaminergic neurotransmission using microdialysis in freely moving rats

Paraoxon (PDX) is an extremely neurotoxic organophosphorous compound (OP) which main toxic mechanism is the irreversible inhibition of cholinesterase. Although the cholinergic system has always been linked as responsible for its acute effects, experimental studies have suggested that the dopaminergic system also may be a potential target for OPs. Based on this, in this study, the acute intrastriatal effects of PDX on dopaminergic neurotransmission were characterized in vivo using brain microdialysis in freely moving rats. In situ administration of PDX (5, 25 and 50 nmol, 60 min) significantly increased the striatal dopamine overflow (to 435 +/- 79%, 1066 +/- 120%, and 1861 +/- 332%, respectively), whereas a lower concentration (0.5 nmol) did not affect dopamine levels. Administration of PDX (25 nmol) to atropine (15 nmol) pretreated animals, produced an increase in dopamine overflow that was similar to 63% smaller than those observed in animals not pretreated. Administration of PDX (25 nmol) to mecamylamine (35 nmol) pretreated animals did not significantly affect the PDX-induced dopamine release. Our results suggest that acute administration of PDX increases the dopamine release in a concentration-dependent way, being this release dependent on acetylcholinesterase inhibition and mediated predominantly by the activation of striatal muscarinic receptors, once the muscarinic antagonist atropine partially blocks the PDX-induced dopamine release.