Figure 2.
3,4-Methylenedioxymethamphetamine (MDMA) pre-treatment has prolonged and generalized effects on extinction. MDMA (7.8 mg kg−1) was administered 30 min before re-exposure to the CS tone on Day 3. (a) MDMA-treated mice exhibited a greater reduction in freezing to four CS tones 10 days later (t(14)=3.05, P=0.0093 for effect of treatment; n=8 per group). (b) MDMA-treated animals exhibited reduced freezing to four CS tones when tested outside of the extinction context 24 h later. (t(14)=4.45, P=0.0006 for effect of treatment; n=8 per group). (c) The effect of MDMA pre-treatment on the response to a single CS-tone re-exposure was tested. MDMA reduced freezing during re-activation (t(8)=2.77, P=0.0122 for effect of treatment; n=5 per group) but did not affect conditioned freezing the following day (t(8)=0.66, P=0.2633 for effect of treatment; n=5 per group). (d) Animals were conditioned to four CS–US pairings (0.6 mA, 0.5 s). MDMA administered before extinction training with 14 CS tones significantly reduced conditioned freezing during the extinction session (t(16)=2.21, P=0.0280 for effect of MDMA; n=8–10 per group) and 24 h later when animals were tested with 14 CS tones (t(16)=2.679, P=0.0150 for effect of MDMA; n=8–10 per group). (e) MDMA-treated animals exhibited significantly less freezing during the first six CS exposures of prolonged extinction training (F(1,16)=5.80, P=0.0280 for between-subject effect of treatment). (f) Pre-extinction MDMA reduced conditioned freezing the following day (F(1,16)=7.24, P=0.0150 for between-subject effect of treatment). Bars represent mean±s.e. values of %freezing. *P<0.05, ^P<0.01, #P<0.001. CS, conditioned stimulus; US, unconditioned stimulus.