Roles of pedunculopontine tegmental cholinergic receptors in brain stimulation reward in the rat

Rationale: The brainstem pedunculopontine tegmental nucleus (PPTg) is proposed to mediate hypothalamic self-stimulation reward via cholinergic activation of the ventral tegmental area (VTA). However, to date there is little direct evidence to support this hypothesis. Objectives: To further study the role of PPTg in hypothalamic self-stimulation reward. Methods: By using in vivo microdialysis, the levels of extracellular acetylcholine (ACh) in the PPTg and VTA were detected during lateral hypothalamic (LH) self-stimulation in rats. Rate-frequency curve shift procedure was used to evaluate the effects of nonselective muscarinic antagonist scopolamine (1 similar to 100 mu g/mu l) and nicotinic antagonist mecamylamine (5 similar to 100 mu g/mu l) microinjected into the PPTg on the rewarding efficacy of LH self-stimulation. Subsequently, the drugs were injected into the PPTg, and the extracellular ACh in the VTA was measured. Results: LH self-stimulation produced a concurrent ACh release in the PPTg and VTA. Intra-PPTg injection of scopolamine (100 mu g/mu l) significantly reduced the frequency threshold for LH self-stimulation reward, but nicotinic antagonist mecamylamine did not shift the threshold. However, mecamylamine (10, 25 mu g/mu l) injected into the PPTg robustly diminished the nicotine-potentiated LH self-stimulation reward. The extracellular ACh in the VTA was dramatically increased by intra-PPTg scopolamine (10, 100 mu g/mu l), but not by mecamylamine. Conclusions: Results confirm that PPTg plays an important role in brain stimulation reward by modulating the cholinergic activity of the VTA. The PPTg muscarinic receptors contribute to an inhibitory modulation of reward effects by self-stimulation, whereas nicotinic receptors seem to be more involved in nicotine potentiation of brain stimulation reward.