A series of experiments were conducted to investigate the role of presynaptic dopamine (DA) and noradrenaline (NA) neurotransmission in stimulant-unconditioned locomotion and defecation. (+)-Amphetamine (AMP, 1.5 mg/kg, s.c.) increased both locomotion and defecation in rats, and both of these effects were conditioned to environmental stimuli. Some groups of rats were treated with DSP4 (50 mg/kg, i.p.), a selective, long-lasting NA neurotoxin, given 7 days prior to conditioning with AMP. This treatment depleted forebrain NA to between 1% and 54% of control levels, depending on the brain region, but did not attenuate either AMP-unconditioned or conditioned locomotion. These results indicate that NA does not mediate either AMP unconditioned or conditioned locomotion. α-Methyl-para-tyrosine methyl ester (αMPT, 25-50 mg/kg, s.c.), a selective inhibitor of catecholamine synthesis given during conditioning with AMP, attenuated unconditioned AMP-induced locomotion and defecation but did not influence AMP-conditioned locomotion and defecation. Thus, αMPT blocked AMP-induced unconditioned locomotion, supporting the hypothesis that the locomotor and defecation stimulant effects of AMP are mediated by DA release. In spite of the attenuation of the direct effects of AMP, αMPT did not attenuate AMP-conditioned locomotion or defecation. It is concluded that AMP-induced release of dopamine is responsible for the unconditioned behavioral effects of amphetamine but not for the conditioning of amphetamine-induced locomotion and defecation.