Acute food deprivation reverses morphine-induced locomotion deficits in M₅ muscarinic receptor knockout mice

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• 作者：Stephan Steidl ; Esther Lee ; David Wasserman ; John S. Yeomans
• 关键词：CPP ; conditioned place preference ; FD ; food-deprived ; GABA ; gamma-aminobutyric acid ; LDT ; laterodorsal tegmental nucleus ; ND ; non-deprived ; PPT ; pedunculopontine tegmental nucleus ; SNc ; substantia nigra&mdash ; pars compacta ; VTA ; ventral tegmental area
• 刊名：Behavioural Brain Research
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：252
• 期：Complete
• 页码：176-179
• 全文大小：741 K

文摘

Lesions of the pedunculopontine tegmental nucleus (PPT), one of two sources of cholinergic input to the ventral tegmental area (VTA), block conditioned place preference (CPP) for morphine in drug-na?ve rats. M₅ muscarinic cholinergic receptors, expressed by midbrain dopamine neurons, are critical for the ability of morphine to increase nucleus accumbens dopamine levels and locomotion, and for morphine CPP. This suggests that M₅-mediated PPT cholinergic inputs to VTA dopamine neurons critically contribute to morphine-induced dopamine activation, reward and locomotion. In the current study we tested whether food deprivation, which reduces PPT contribution to morphine CPP in rats, could also reduce M₅ contributions to morphine-induced locomotion in mice. Acute 18-h food deprivation reversed the phenotypic differences usually seen between non-deprived wild-type and M₅ knockout mice. That is, food deprivation increased morphine-induced locomotion in M₅ knockout mice but reduced morphine-induced locomotion in wild-type mice. Food deprivation increased saline-induced locomotion equally in wild-type and M₅ knockout mice. Based on these findings, we suggest that food deprivation reduces the contribution of M₅-mediated PPT cholinergic inputs to the VTA in morphine-induced locomotion and increases the contribution of a PPT-independent pathway. The contributions of cholinergic, dopaminergic and GABAergic neurons to the effects of acute food deprivation are discussed.