Stimulation of rat striatal tyrosine hydroxylase activity following intranigral administration of sigma receptor ligands.

The effects of sigma ligands on turning behavior and striatal tyrosine hydroxylase activity were determined following microinjection of two chemically dissimilar sigma ligands into the rat substantia nigra. Striatal tyrosine hydroxylase activity was monitored by measuring the amount of 3,4-dihydroxyphenylalanine (DOPA) formed following inhibition of DOPA decarboxylase activity with m-hydroxybenzylhydrazine (NSD-1015). The sigma ligands, 1,3-di-o-tolylguanidine (DTG) and (-)-deoxy-N-benzylnormetazocine, produced a significant increase both in contralateral turning and in tyrosine hydroxylase activity. The DTG-induced increase in tyrosine hydroxylase activity was not antagonized by intranigral injection of the NMDA receptor antagonist, 3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP). CPP alone produced significant contralateral turning that was not accompanied by an increase in striatal tyrosine hydroxylase activity, indicating that turning per se is not sufficient to activate striatal tyrosine hydroxylase. The DTG-induced increase in tyrosine hydroxylase activity was antagonized by general anesthetics such as halothane and chloral hydrate. These results indicate that occupancy of sigma receptors in the substantia nigra is associated with an activation of dopamine formation in dopaminergic terminals in the striatum and support the concept that sigma activity in the substantia nigra produces an activation of dopamine-mediated responses in the striatum.