Serial feature positive and feature negative discrimination learning in a taste avoidance preparation: implications for interoceptive control of behavior.

BACKGROUND: Psychoactive drugs produce interoceptive stimuli that can guide appropriate behaviors by initiating or inhibiting responding. OBJECTIVE: The current study investigated whether an interoceptive morphine state produces similar patterns of serial feature positive (FP) and feature negative (FN) discrimination learning under comparable conditions in a taste avoidance design. METHODS: Male Sprague-Dawley rats were trained under 10 cycles of FP or FN discrimination. In the FP task, morphine (10 mg/kg, IP) signaled that a saccharin solution was followed by LiCl (1.2 mEq, IP), while the vehicle (saline) signaled that the LiCl was withheld. In the FN task, the contingency was reversed. RESULTS: The FP-trained rats acquired the discrimination after three training cycles, consuming significantly less saccharin on morphine, than on vehicle, sessions ( P  < 0.05). The FN-trained rats acquired the discrimination after six training cycles, consuming more on morphine than on vehicle sessions ( P < 0.05). However, FN-trained rats never recovered saccharin consumption to baseline levels and 40% of the rats continued to avoid saccharin (consuming 0 ml) on morphine sessions. Control rats that never received LiCl consumed high levels of saccharin on morphine and vehicle sessions, indicating that morphine did not produce unconditioned suppression of saccharin consumption. CONCLUSION: The difficulty to acquire FN discrimination might reflect the limitations of learning about safety contingencies in the taste avoidance design. The rapidity of FP learning when a drug state signals an aversive contingency may have implications for the general role of interoceptive stimuli in the control of behavior.

Methylone pre-exposure differentially impacts the aversive effects of MDPV and MDMA in male and female Sprague-Dawley rats: Implications for abuse vulnerability.

BACKGROUND: Polydrug use is well documented in synthetic cathinone users, although the consequences of such use are not well characterized. In pre-clinical research, a pre-exposure to a drug has been reported to attenuate the aversive effects of other drugs which has implications for their abuse potential. The goal of the present study was to investigate the impact of pre-exposure to the synthetic cathinone methylone on the aversive effects of MDPV and MDMA. METHOD: Male and female Sprague-Dawley rats were exposed to 10 mg/kg of methylone every 4th day (for a total of five injections) prior to taste avoidance training with 1.8 mg/kg of MDPV or 1 mg/kg of MDMA. RESULTS: MDPV and MDMA induced taste avoidance in males and females (all p's < 0.05). In males, methylone pre-exposure attenuated the avoidance induced by MDPV and MDMA (all p's < 0.05) with the attenuation greater with MDPV. In females, methylone pre-exposure attenuated avoidance induced by MDPV (all p's < 0.05), but it had no effect on those induced by MDMA (all p's > 0.05). CONCLUSIONS: The effects of exposure to methylone on taste avoidance induced by MDPV and MDMA were drug- (MDPV > MDMA) and sex- (MDMA only in males) dependent. The attenuating effects of methylone pre-exposure on MDPV and MDMA were discussed in terms of their shared neurochemical action. These findings suggest that a history of methylone use may reduce the aversive effects of MDPV and MDMA which may have implications for polydrug use involving the synthetic cathinones.