Anatomical disassociation of amphetamine's rewarding and aversive effects: an intracranial microinjection study

Amphetamine has rewarding properties in some behavioral paradigms, such as self-administration and conditioned place preference (CPP), but an aversive component is also apparent when the drug is tested with the conditioned taste aversion (CTA) paradigm. The present study was an attempt to determine the neuroanatomical substrates of the drug's rewarding and aversive effects. Previous evidence suggested that amphetamine's stimulation of activity in dopaminergic synapses is critical for both effects. Amphetamine was therefore micro-injected bilaterally (10 micrograms/0.5 microliter per side) into six different dopaminergic sites, each in a different group of animals: the medial prefrontal cortex, nucleus accumbens, anteromedial caudate nucleus, lateroventral caudate nucleus, amygdala, and the region subjacent to the area postrema (AP region). The effects of these injections in both the taste and place conditioning paradigms were examined in separate experiments. Of the six sites, a significant CPP was observed only with accumbens injections and a significant CTA was observed only with AP region injections. It was concluded that the accumbens plays a primary role in mediating the rewarding effects of amphetamine and that the AP region plays a primary role in mediating the CTA. This constitutes an anatomical disassociation of amphetamine's rewarding and aversive effects. The differential associative bias of place-reward and taste-aversion learning apparent in the results is discussed.