BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF ACUTE AND REPEATED ADMINISTRATION OF TRIADIMEFON IN THE MALE-RAT

The effects of triadimefon (TDF) were examined in male Sprague-Dawley rats. In this study, the acute administration of TDF (100 mg/kg) was f ound to significantly increase locomotor activity and induce stereotyp ed behavior. Acute administration of TDF was also found to significant ly increase dopamine (DA) and homovanillic acid (HVA) levels while the dihydroxyphenylacetic acid (DOPAC) level remained unchanged in both t he nucleus accumbens (NA) and striatal (ST) tissues when compared to c ontrol. Furthermore, DOPAC: DA ratios were significantly reduced in bo th brain regions suggesting an increase in DA turn overrate. On the ot her hand, in animals receiving repeated TDF administration, only the H VA level was significantly increased in both the ST and NA. TDF neithe r competed for binding to D-2, D-3 or D-4 DA receptors nor altered the K-d or the B-max of PHI SCH 23390 and [H-3] spiperone recognition sit es associated with striatal D-1 and D-2 receptors, respectively. Meanw hile, TDF competed with [H-3] GBR 12935 for binding to DA transporter sites with strong affinity, but repeated treatment with TDF had no sus tained or cumulative effect on the DA transporter system. These result s clearly show that acute TDF-induced behavioral effects may not be vi a binding to DA receptors, but through the interaction with DA transpo rter binding sites. Also, TDF does not appear to produce cumulative ef fects in the parameters evaluated. (C) 1997 Intox Press, Inc.