Amphetamine conditioned cue preference and the neurobiology of drug-seeking

This brief review draws a parallel between the drug-seeking behavior of humans addicted to amphetamine and the preference exhibited by animals for a place in which they have previously experienced the pharmacological effects of the same drug. Anatomical and pharmacological analyses suggest that nucleus accumbens dopamine receptor activation is necessary for the development of this preference. Through connections that synapse in ventral pallidum, a neural representation of accumbens dopamine receptor activation may reach the lateral nucleus of the amygdala where it could become associated with representations of existing environmental cues that also reach the lateral nucleus from cerebral cortex. When these conditioned cues are encountered on future occasions, activation of the amygdala-based association may reach either nucleus accumbens or ventral tegmental area. This neural activation either produces an excess of accumbens dopamine release or acts in synergy with a tonic level of dopamine release to cause the animal to approach and maintain contact with the conditioned cues.