Evidence for presynaptic dopamine mechanisms underlying amphetamine-conditioned locomotion

Area of Science:

• Neuroscience
• Behavioral Pharmacology

Background:

• Amphetamine exposure in a specific environment leads to conditioned psychomotor responses in rats.
• Dopamine receptor antagonists and alpha-methyl-p-tyrosine block unconditioned amphetamine effects but not conditioned locomotion.

Purpose of the Study:

• To investigate the role of dopamine pools in the establishment of amphetamine-conditioned locomotion.
• To differentiate the mechanisms underlying unconditioned and conditioned amphetamine effects.

Main Methods:

• Rats received combined treatment of alpha-methyl-p-tyrosine and amphetamine for 8 days.
• Reserpine was administered alone or in conjunction with alpha-methyl-p-tyrosine and amphetamine.
• Conditioned locomotion was assessed in the drug-paired environment without drug administration.

Main Results:

• Alpha-methyl-p-tyrosine blocked amphetamine-induced locomotion but only attenuated conditioned locomotion.
• Reserpine potentiated amphetamine-induced locomotion and, when combined with alpha-methyl-p-tyrosine, blocked it initially but allowed recovery.
• Reserpine alone did not affect conditioned locomotion, but blocked it when administered with alpha-methyl-p-tyrosine.

Conclusions:

• The alpha-methyl-p-tyrosine-sensitive dopamine pool mediates immediate amphetamine psychomotor effects.
• Both alpha-methyl-p-tyrosine- and reserpine-sensitive dopamine pools are involved in establishing amphetamine-conditioned locomotion.
• Amphetamine-conditioned locomotion is independent of amphetamine's direct locomotor effects.