Footshock facilitates methamphetamine-induced conditioned suppression through HPA axis, not dopamine

- Footshock increases MAMPH-induced conditioned suppression of saccharin intake.
- The HPA axis mediates footshock increases of MAMPH-induced taste suppression.
- D2 receptors did not affect footshock increases of the MAMPH-induced suppression.
- The enhancement of footshock treatments is due to the aversive (not rewarding) effect.

The present study examined whether footshock can enhance methamphetamine (MAMPH)-induced conditioned suppression and whether this effect involves the dopamine (DA) reward system or hypothalamic-pituitary-adrenal (HPA) axis. We also examined whether the footshock-induced enhancements of MAMPH-induced conditioned suppression are attributable to MAMPH's rewarding or aversive properties. During the footshock phase, all female rats received 0.1 mg/kg haloperidol (HAL) and its vehicle (2% tartaric acid solution), or low and high doses of dexamethasone (DEX; 0.5 and 1.0 mg/kg) and its vehicle before each footshock (1 mA, 2 s), or no footshock, in seven trials once per day. The control group did not receive any drugs or footshocks. All of the rats were then allowed 15 min access to a 0.1% saccharin solution and then received 2 mg/kg MAMPH in five trials once per day. Footshock exhibited an increase in MAMPH-induced taste suppression. The low- and high-dose DEX groups but not the HAL group exhibited a blocking effect of the footshock enhancements of MAMPH-induced taste suppression. The low- and high-dose DEX groups exhibited a significant decrease in corticosterone levels during the footshock treatment phase but not during the testing phase. Altogether, the HPA stress system and not the DA reward system, particularly D2 receptors, appear to mediate the footshock-induced enhancements of MAMPH-induced conditioned taste suppression, which may result from the aversive and not the rewarding properties of MAMPH. The present findings may provide some clinical implications for alternating aversively classical conditioning for psychiatric disorders.