Acute apocynin-tandospirone derivatives (ATDs) exacerbate methamphetamine-induced hyperlocomotion in rats

Apocynin-tandospirone derivatives (ATDs) have recently been shown to ameliorate methamphetamine (MAP)-induced behavioral abnormalities when administered chronically, presumably through antioxidant and interneuron-related mechanisms. However, their acute behavioral profile remains unclear.

In this study, we examined whether acute ATD administration exerts antipsychotic-like effects in rats.

Rats received acute treatment with ATDs (A-2, A-3, A-4), atypical antipsychotics, or saline, followed by assessments of spontaneous locomotor activity and MAP-induced hyperlocomotion. Prepulse inhibition (PPI), dopamine (DA) concentrations in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAC) were also measured.

Acute ATD administration did not reduce spontaneous activity and failed to suppress MAP-induced hyperlocomotion. Instead, all three ATDs significantly enhanced MAP-induced locomotor responses, with A-3 showing dose-dependent potentiation. ATDs did not improve MAP-induced PPI deficits, except for a modest effect of high-dose A-3. Consistent with these behavioral outcomes, DA levels in the NAC were unchanged, and only small increases in mPFC DA were observed with A-2 and high-dose A-3.

The results demonstrate that acute ATD administration neither suppressed MAP-induced behavioral abnormalities nor produced marked neurochemical changes, but instead enhanced MAP-induced locomotor activity, indicating a clear dissociation from their previously reported chronic effects.