Expression of behavioral sensitization to the cocaine-like fungicide triadimefon is blocked by pretreatment with AMPA, NMDA and DA D1 receptor antagonists

Abstract

Triadimefon (TDF) is a triazole fungicide that blocks the reuptake of dopamine (DA), much like cocaine. A recent study in our laboratory found that intermittent injections of TDF led to robust locomotor sensitization in response to challenge TDF after a 2-week withdrawal period. The current study sought to determine whether the expression of TDF behavioral sensitization could be prevented by the DA D1-like receptor antagonist SCH 23390 (SCH), the DA D2-like receptor antagonist remoxipride (Rem), the competitive NMDA antagonist CPP, or the AMPA antagonist NBQX. Adult male C57/BL6 mice were injected with vehicle or 75 mg/kg TDF twice a week for 7 weeks, with locomotor activity measured periodically across the 14 doses. After a 2-week withdrawal period, mice were pretreated with SCH (0.015 mg/kg), Rem (0.3 mg/kg), CPP (2.5 mg/kg) or NBQX (10.0 mg/kg) followed 30 min later by vehicle or 75 mg/kg TDF and tested for the expression of TDF sensitization. Intermittent administration of TDF led to the development and robust expression of behavioral sensitization in terms of vertical activity. Pretreatment with SCH, NBQX and CPP successfully blocked the expression of vertical sensitization to TDF, while Rem pretreatment did not. All four antagonists, however, attenuated the neurochemical changes normally associated with TDF sensitization as measured 8 h after the 2-week TDF challenge. This paper reveals that NMDA, AMPA and DA D1-like receptors are necessary for the behavioral expression of sensitization to the fungicide triadimefon.