Increases in rat striatal extracellular dopamine and vacuous chewing produced by two sigma receptor ligands

The present studies were carried out to analyze the neurochemical and behavioral effects of peripheral sigma ligand administration in the rat. Based upon previous studies which showed an increase in turning behavior following unilateral intranigral administration of sigma ligands, we determined the effects of two sigma ligands, 1,3-di-o-tolylguanidine (DTG) and (+)-pentazocine, on extracellular dopamine levels in the rat striatum. Dopamine levels were monitored via microdialysis in awake freely moving animals following i.p. injection of the ligands. Both DTG (1 and 3 mg/kg) and (+)-pentazocine (10 mg/kg) produced a significant (30-50%) increase in extracellular dopamine. Given the relatively high concentration of sigma receptors in brain nuclei involved in facial and mouth movements, we have also determined the effects of the two sigma ligands on facial movements. Both ligands produced a significant increase in vacuous chewing movements, suggesting that studies on the consequences of sigma receptor activation may have relevance to animal models of human dystonia and/or dyskinesia.