title: Acute food deprivation reverses morphine-induced locomotion deficits in M5 muscarinic receptor knockout mice.
abstract: 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-naïve 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.
authors.affiliation: Department of Psychology, University of Toronto, 100 Saint George Street, Toronto, Ontario M5S 3G3, Canada. ssteidl@luc.edu
authors.forename: Stephan
authors.initials: S
authors.lastname: Steidl
authors.forename: Esther
authors.initials: E
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Wasserman
authors.forename: John S
authors.initials: JS
authors.lastname: Yeomans
mesh_terms: D000818:Animals; D005508:Food Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000009:adverse effects*; D009069:Movement Disorders / Q000209:etiology*; D009294:Narcotics / Q000009:adverse effects*; D043642:Receptor, Muscarinic M5 / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
chemical_list: D009294:Narcotics; D043642:Receptor, Muscarinic M5; D009020:Morphine
keywords: Acetylcholine; CPP; Dopamine; FD; GABA; LDT; Laterodorsal tegmental nucleus; Motivation; ND; Opiates; PPT; SNc; VTA; Withdrawal; conditioned place preference; food-deprived; gamma-aminobutyric acid; laterodorsal tegmental nucleus; non-deprived; pedunculopontine tegmental nucleus; substantia nigra—pars compacta; ventral tegmental area