AIM:To examine whether the ob/ob mouse model of obesity is accompanied by enteric nervous system ab-normalities such as altered motility METHODS:The study examined the distribution of the P2X 2 receptor (P2X 2 R) in myenteric neurons of female ob/ob mice. Specifically, we used immunohistochemistry to analyze the co-expression of the P2X 2 R with neuronal nitric oxide synthase (nNOS), choline acetyltrans-ferase (ChAT), and calretinin (CalR) in neurons of the small intestine myenteric plexus in ob/ob and control female mice In these sections, we used scanning confocal microscopy to analyze the co-localization of these markers as well as the neuronal density (cm 2 ) and area profile (μm2) of P2X 2 R-positive neurons In addition, enteric neurons were labeled using the nicotinamide adenine dinucleotide (NA H) diaphorase method and analyzed with light microscopy as an alternate means by which to analyze neuronal density and areaRESULTS:In the present study, we observed a 29 6% increase in the body weight of the ob/ob animals (OG) compared to the control group (CG) In addition, the average small intestine area was increased by approxi-mately 29 6% in the OG compared to the CG Immu-noreactivity (IR) for the P2X 2 R, nNOS, ChAT and CalR was detectable in the myenteric plexus, as well as in the smooth muscle, in both groups This IR appeared to be mainly cytoplasmic and was also associated with the cell membrane of the myenteric plexus neurons, where it outlined the neuronal cell bodies and their processes P2X 2 R-IR was observed to co-localize 100% with that for nNOS, ChAT and CalR in neurons of both groups In the ob/ob group, however, we observed that the neuronal density (neuron/cm 2 ) of P2X 2 R-IR cells was in-creased by 62% compared to CG, while that of NOS-IR and ChAT-IR neurons was reduced by 49% and 57%, respectively, compared to control mice The neuronal density of CalR-IR neurons was not different between the groups Morphometric studies further demonstrated that the cell body profile area (μm2) of nNOS-IR, ChAT-IR and CalR-IR neurons was increased by 34%, 20% and 55%, respectively, in the OG compared to controls Staining for NA H diaphorase activity is widely used to detect alterations in the enteric nervous system; however, our qualitative examination of NA H-diaphorase positive neurons in the myenteric ganglia revealed an overall similarity between the two groups CONCLUSION:We demonstrate increases in P2X2R expression and alterations in nNOS, ChAT and CalR IR in ileal myenteric neurons of female ob/ob mice compared to wild-type controls. AIM: To examine whether the ob / ob mouse model of obesity is accompanied by enteric nervous system ab-normalities such as altered motility METHODS: The study examined the distribution of the P2X 2 receptor (P2X 2 R) in myenteric neurons of female ob / ob mice. Specifically, we used immunohistochemistry to analyze the co-expression of the P2X 2 R with neuronal nitric oxide synthase (nNOS), choline acetyltrans-ferase (ChAT), and calretinin (CalR) in neurons of the small intestine myenteric plexus in ob / ob and control female mice In these sections, we used scanning confocal microscopy to analyze the co-localization of these markers as well as the neuronal density (cm 2) and area profile (μm2) of P2X 2 R-positive neurons in addition , enteric neurons were labeled using the nicotinamide adenine dinucleotide (NA H) diaphorase method and analyzed with light microscopy as an alternate means by which to analyze neuronal density and areaRESULTS: In the present study, we observed a 29 6% increase in t he body weight of the ob / ob animals (OG) compared to the control group (CG) In addition, the average small intestine area was increased by approxi- mately 29 6% in the OG compared to the CG Immu-noreactivity (IR) for the P2X 2 R, nNOS, ChAT and CalR was detectable in the myenteric plexus, as well as in the smooth muscle, in both groups This IR was be mainly cytoplasmic and was also associated with the cell membrane of the myenteric plexus neurons, Where it outlined the neuronal cell bodies and their processes P2X 2 R-IR was observed to co-localize 100% with that for nNOS, ChAT and CalR in neurons of both groups In the ob / ob group, however, we observed that the neuronal density (neuron / cm 2) of P2X 2 R-IR cells was in-creased by 62% compared to CG, while that of NOS-IR and ChAT-IR neurons was reduced by 49% and 57%, respectively, compared to control mice The neuronal density of CalR-IR neurons was not different between the groups Morphometric studies further demonstrated that th eCell body profile area (μm2) of nNOS-IR, ChAT-IR and Cal-R neurons was increased by 34%, 20% and 55%, respectively, in the OG compared to controls Staining for NA H diaphorase activity is widely used to detect alterations in the enteric nervous system; however, our qualitative examination of NA H-diaphorase positive neurons in the myenteric ganglia revealed an overall similarity between the two groups CONCLUSION: We demonstrate increases in P2X2R expression and alterations in nNOS, ChAT and CalR IR in ileal myenteric neurons of female ob / ob mice compared to wild-type controls.