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Reversal of Morphine-induced Locomotion in M5 Muscarinic Receptor Knockout Mice with Food Deprivation but not Bilateral Infusions of VTA BDNF

Cholinergic inputs from mesopontine tegmentum activate midbrain dopamine (DA) neurons via M5 muscarinic receptors. The M5 receptor is important for mesopontine stimulation-induced accumbal or striatal DA efflux, brain stimulation reward or morphine-induced conditioned place preference (CPP). M5 receptor knockout (KO) mice show 40-50% less morphine-induced locomotion. Pedunculopontine tegmental nucleus (PPT) lesions in rodents block morphine CPP, but are ineffective after 18 hours food deprivation, opiate dependence, or intra-VTA BDNF. Based on these findings, we investigated whether acute food deprivation or intra-VTA BDNF alters morphine-induced locomotion (3 and 10 mg/kg, i.p.) in C57BL/6 M5 KO mice. Non-deprived M5 KOs showed reduced morphine-induced locomotion, suggesting M5 receptors partly mediate morphine-induced locomotion. Morphine-induced locomotion was reversed in food-deprived mice, suggesting the stimulant effects of morphine were altered to bypass the PPT. Unexpectedly, intra-VTA BDNF infusions were ineffective in altering morphine-induced locomotion. Additionally, M5 KOs receiving intra-VTA saline showed no deficits in morphine-induced locomotion.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25752
Date07 January 2011
CreatorsLee, Esther
ContributorsYeomans, John S.
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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