The present study used the conditioned place preference (CPP) paradigm to examine the neural mechanisms underlying morphine's rewarding effect in the rat. Of thirteen sites tested with intra-cerebral morphine injections, only the ventral tegmental area (VTA) and periaqueductal gray (PAG) produced a CPP, suggesting that morphine's rewarding effect is initiated by an action at these sites. The CPPs induced by intra-VTA and intra-PAG morphine may be produced by different mechanisms because animals conditioned with these two injections exhibited different patterns of behaviour during testing. Injections of a quaternary opioid antagonist into either the VTA or PAG blocked a CPP to systemic morphine, confirming that opiate-induced reward is mediated via opioid receptors in these sites. Lesions of the pedunculopontine tegmental nucleus (PPT$ rm sb{g}),$ ventral striatum (VS), PAG, or fornix reduced a CPP to morphine, although PAG and fornix lesioned animals displayed a CPP when tested in a drugged state. These findings suggest that PPT$ rm sb{g}$ and VS lesions reduce the rewarding effect of morphine, and that PAG and fornix lesions disrupt the ability to retrieve information about the relationship between conditioned and unconditioned stimuli.

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The pedunculopontine tegmental nucleus (PPTg) has been proposed to be critical in drug and food reward. It is a major source of cholinergic inputs to the substantia nigra and ventral tegmental area, areas important in reward, and is believed to modulate activity of dopamine neurons through a cholinergic mechanism. The firing rate of cholinergic PPTg cells is regulated by muscarinic autoreceptors that can be blocked to increase cell firing. If the PPTg modulates dopamine neurons involved in reward, then a muscarinic antagonist microinjected into the PPTg should be rewarding. To test this hypothesis, bilateral microinjections of scopolamine methyl bromide (5 $ mu$g or 20 $ mu$g) or 0.9% saline were used as reward treatments in the conditioned place preference test. On the test day, rats from both doses of drug avoided the drug-paired chamber, which suggests that cholinergic PPTg cells are not involved in reward.

This thesis explored whether interpretations of the reinforcing effect of stimulation trains used in the self-administration of brain-stimulation (SABS) paradigm were artifacts of the reinforcement schedule chosen or whether it represented a genuine attempt by animals to maintain optimal levels of reward. Results demonstrate that stimulation trains used in SABS are reinforcing and that animals regulate pulse frequency to optimize the level of reward. The thesis then explored whether pedunculopontine tegmental nucleus (PPTg) lesions blocked the acquisition or maintenance of SABS, and the acquisition of eight-arm radial maze learning. Results showed that lesions confined to the PPTg block acquisition and maintenance of SABS, suggesting that the PPTg mediates the positive reinforcing effects of BSR. Further, PPTg lesions blocked win-shift and win-stay radial maze learning. However, results indicate that animals were not impaired in "shifting" or "staying" behavior. It is speculated that PPTg lesions block the reinforcing effects of food, which produce inefficient performance on both memory tasks.

It has been proposed that analgesia in the formalin test is mediated through forebrain systems associated with reinforcement, whereas motor responses necessary for the expression of pain are organized at the level of the brainstem. Because it is located in the brainstem and connected with both limbic reward systems and motor structures, the pedunculopontine tegmental nucleus (PPTg) is a site where reward signals might influence the expression of pain. Experiment 1 confirmed that NMDA-induced lesions of the PPTg block the development of a conditioned place preference to morphine. Subsequently, morphine-induced analgesia was found to be reduced, but not eliminated. The reduction of reward was not significantly correlated with loss of choline acetyltransferase containing neurons in the PPTg. In Experiment 2, PPTg lesions did not affect morphine analgesia in drug naive animals, but produced motor abnormalities and blocked the morphine-induced depression of spontaneous motor activity and catalepsy.

The role of the pedunculopontine tegmental nucleus (PPTg) in motivation and cognitive functions is controversial. In order to clarify the involvement of this nucleus in learning, rats with N-methyl-D-Aspartate (NMDA) lesions to the PPTg were tested on the acquisition of a delayed non-matching to position task (DNMP) performed in a T-maze. Unlike sham-lesioned rats, animals with PPTg lesions did not learn the task. Analysis of the behavior displayed by the lesions animals, however, suggested that these rats suffered from elevated emotionality or arousal, rather than from learning deficits. This hypothesis was confirmed by demonstrating that the anxiolytic compound diazepam (1 mg/kg) normalized the performance of the PPTg-lesioned rats on the DNMP task and reduced the indices of anxiety displayed by animals with PPTg lesions when tested on the elevated plus maze. / These results suggested the possibility that the motivational impairments reported to be induced by PPTg lesions, could also be an artifact of lesion-induced elevation of anxiety or arousal. Thus, in order to verify this hypothesis, it was tested whether diazepam would modify the expression of conditioned place preference (CPP) to morphine and amphetamine in animals with NMDA-induced lesions to the PPTg. Diazepam reversed the effects of the lesion on a morphine CPP but not on an amphetamine CPP. A series of experiments, aimed at characterizing the effects of diazepam on morphine and amphetamine reinforcement in normal rats, showed that diazepam, either systemic or injected in the nucleus accumbens, blocks the reinforcing effects of amphetamine but has no effect on the reinforcing effects of morphine. These results suggest that impairments in CPP learning caused by PPTg lesions do not result from motivational deficits, but are caused by elevated emotionality or abnormal arousal.

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