| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
We investigated the role of cholinergic pathway that projects from mesopontine tegmentum, i.e., pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg), to ventral tegmental area (VTA), in the rat brain reward system.
Using double immunostaining for Fos as a marker of neuronal activity and choline acetyltransferase as a marker of cholinergic neurons, we investigated whether or not intracranial self stimulation (ICSS) of the medial forebrain bundle (MFB) induces Fos expression within PPTg and LDTg. ICSS of the MFB for one hour induced a large increase in the number of cells that expressed Fos in both the LDTg and PPTg, when compared to control brains. However, most of choline acetyltransferase positive cells in these regions did not express Fos. We also examined, using microdialysis, whether ICSS of the MFB increases acetylcholine efflux in the VTA, a terminal region of the mesopontine tegmentum cholinergic pathway. One-hour ICSS significantly increased acetylcholine efflux in the VTA. The results indicate that ICSS of the MFB may increase terminal acetylcholine release without affecting expression of Fos within cell bodies in the cholinergic pathway of the mesopontine tegmentum.
Next, we used the rate-frequency curve-shift procedure to evaluate the effect of nicotinic blockers on the threshold of ICSS reward. The rats were implanted with an electrode in the MFB and an ipsilateral guide cannula in the VTA. Nicotine blockers were continuously infused through reverse dialysis into the VTA two hours before and during the self-stimulation. Mecamylamine (25-100 mM), the channel blocker of nicotinic acetylcholine receptors, sifted rate-frequency curves to the right by a mean of 14.6-35.5% in a dose-related manner. Mecamylamine decreased maximum bar-pressing rates when the shifts were large. Thus, nicotinic receptors in the VTA seem to be important for the mediation of the rewarding effect of the ICSS in rats.
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