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

• Main Author: Lee, Esther
• Other Authors: Yeomans, John S.
• Language: en_ca
• Published: 2010
• Subjects: muscarinic; M5; acetylcholine; dopamine; food deprivation; knockout; mice; morphine; locomotion; brain-derived neurotrophic factor; mesolimbic; pedunculopontine tegmental nucleus; open-field; Neuroscience 0317
• Online Access: http://hdl.handle.net/1807/25752

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.