An examination of d-amphetamine self-administration in pedunculopontine tegmental nucleus-lesioned rats

The pedunculopontine tegmental nucleus (PPTg) has long been suggested to have a role in reward-related behaviour, and there is particular interest in its possible role in drug reward systems. Previous work found increased i.v. self-administration (IVSA) of d-amphetamine following PPTg lesions when training had included both operant pre-training and priming injections. The present study examined the effect of excitotoxin lesions of the PPTg on d-amphetamine IVSA under three training conditions. Naive: no previous experience of d-amphetamine or operant responding. Pre-trained: given operant training with food before lesion surgery took place. Primed: given single non-contingent d-amphetamine infusion (0.1 mg/0.1 ml) at the start of each session. Rats in all conditions were given either ibotenate or phosphate buffer control lesions of the PPTg before d-amphetamine (0.1 mg/0.1 ml infusion) IVSA training took place. Rats received eight sessions of training under a fixed ratio (FR2) schedule of d-amphetamine IVSA, followed by four sessions under a progressive ratio (PR5) schedule. In the naive condition, PPTg-lesioned rats were attenuated in their responding under FR2, and took significantly fewer infusions under PR5 than the control group. Under FR2 in the pretrained condition, there was no difference between PPTg excitotoxin and control lesioned rats; however, PPTg-lesioned rats took significantly fewer infusions under the PR5 schedule. In the primed condition, there were no differences between PPTg-lesioned and control rats under either FR2 or PR5 schedules. These data demonstrate that operant training prior to PPTg lesion surgery corrects some, but not all, of the deficits seen in the naive condition. PPTg-lesioned rats in both naive and pre-trained conditions showed reduced responding for d-amphetamine under a PR5 schedule. These deficits are overcome by priming with d-amphetamine. We suggest that alterations in striatal dopamine activity following PPTg lesions underlie these effects. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.