MDMA enhances associative and nonassociative learning in the rabbit.

The rate of associative learning was assessed in the presence of saline versus methylenedioxymethamphetamine (MDMA) at doses of 0.95, 1.9, and 3.8 mg/kg. The conditioned stimuli (CSs) were lights and tones and the unconditioned stimulus (US) was a corneal air puff. Learning was enhanced by all but the highest dose of drug tested, and the enhancement was most pronounced when light was used as the conditioned stimulus. Nonassociative responding was assessed using unpaired presentations of the lights, tones, and air puffs. MDMA (1.9 mg/kg) produced a slight increase in the percentage of baseline responses but failed to produce an increase in the frequency of nonassociative responding in the presence of the lights or tones. MDMA produced a significant increase in the amplitude of the unconditioned response to the corneal air puff across the 10 sessions. This increase was taken as evidence for sensitization of the unconditioned response, a nonassociative learning phenomenon. In summary, MDMA, like the parent compound methylenedioxyamphetamine (MDA), enhances both conditioned and unconditioned responding. Because this dual effect has not been seen with related psychedelic compounds, the effect appears to be unique to this class of phenylethylamine drugs.