N-methyl-D-aspartate lesions of the pedunculopontine nucleus block acquisition and impair maintenance of responding reinforced with brain stimulation.

Excitotoxin lesions of the pedunculopontine tegmental nucleus have been found to block the acquisition of a conditioned place preference induced by morphine or amphetamine, and it has been suggested that such lesions may attenuate the primary reinforcing effects of these drugs and, possibly, other reinforcers. The present study examined the effects of pedunculopontine lesions on the reinforcing effects of brain stimulation. N-methyl-D-aspartate-induced lesions of the pedunculopontine nucleus prevented spontaneous acquisition of lever pressing for brain stimulation reinforcement during five daily 1 h sessions of training. The effective lesions damaged the retrorubral fields in addition to the pedunculopontine tegmental nucleus. N-methyl-D-aspartate (25 or 50 nmol) lesions of the retrorubral fields did not block acquisition of self-stimulation, however, controls reached their maximum rate of responding in the first session, responding of rats with retrorubral field lesions gradually increased over five days. When excitotoxin-induced lesions of the pedunculopontine nucleus were made after acquisition of self-stimulation, lesioned rats continued to respond to brain stimulation, but at a lower rate than controls. The results show that pedunculopontine lesions interfere with the learning and expression of a response reinforced by brain stimulation just as they block learning motivated by drugs and natural rewards. They also suggest that collateral damage to the retrorubral fields may contribute to the effects of pedunculopontine lesions on reinforced behaviour. These data support the view that the pedunculopontine tegmental nucleus is involved in the process by which reinforcers control purposive behaviour.