Effects of pedunculopontine tegmental nucleus lesions on morphine-induced conditioned place preference and analgesia in the formalin test

Abstract

The development of a conditioned place preference to morphine (2 mg/kg; three pairings) and the analgesic effect of morphine (0, 4 or 8 mg/kg) in the formalin test were studied in rats with sham or neurotoxin lesions of the pedunculopontine tegmental nucleus. Lesions were induced by bilateral infusions of N-methyl- d-aspartate (0.5 μ1 of 0.1 M solution) or vehicle over 10 min. No anti-seizure medication was administered in the first experiment, whereas animals in the second experiment were injected with diazepam (1 mg/kg) immediately after surgery. In Experiment 1, behaviour in the conditioned place preference and formalin tests was assessed in separate groups of lesioned and control rats. In Experiment 2, the same animals received both sets of tests. In both experiments lesions of the pedunculopontine tegmental nucleus blocked the development of a conditioned place preference to morphine, but had no effect on the behavioural response to formalin, or on its inhibition by morphine. Examination of cholinergic-stained cells found no correlation between the magnitude of behavioural effects and the number of acetylcholine cells destroyed by the lesions. These results confirm that the pedunculopontine tegmental nucleus mediates the development of a morphine-induced conditioned place preference, but not the analgesic effect of morphine.