Amphetamine enhancement of reward asymmetry

Rats with bilaterally implanted lateral hypothalamic electrodes were tested daily for self-stimulation to each side of the brain; rotation (circling behavior) was recorded concomitantly. All rats rotated in a perferred direction regardless of the side of the brain stimulated and all rats had asymmetries in self-stimulation sensitivity (threshold and rate-intensity functions) related to the direction of rotation. Amphetamine both enhanced rotation and potentiated the asymmetry in self-stimulation sensitivity. Subsequently rats were tested in a choice procedure providing concurrent access to rewarding stimulation of either side of the brain; currents were titrated such that, under baseline conditions, rats continually alternated between self-stimulating one side of the brain or the other. Amphetamine induced a robust preference for stimulation to the more sensitive side of the brain (the side having a lower threshold). The results are discussed in relation to mechanisms of drug reinforcement and to biological etiologies of schizophrenia. It is proposed that schizophrenia results from a lateralized overactivity of dopaminergic neuronal systems mediating reward and that amphetamine mimics schizophrenic symptomatology by enhancing lateralization of the same systems.