title: Impaired cued and spatial learning performance and altered cannabinoid CB₁ receptor functionality in the substantia nigra in a rat model of diabetic neuropathy.
abstract: Diabetes, and associated diabetic neuropathic pain, impact negatively on cognitive function. However, the underlying mechanisms remain poorly understood. This study investigated neuropathic pain-related behaviour and cognitive function in the rat streptozotocin (STZ) model of diabetes, and assessed cannabinoid1 (CB1) receptor functionality in discrete brain regions. Male Lister-Hooded rats received STZ (60 mg/kgs.c.) or vehicle. Sensory responses were assessed in von Frey and Hargreaves tests. Cognitive, motor and sensorimotor functions were assessed using novel object recognition and Morris water maze tasks. CB1 receptor functionality was assessed by [(35)S]GTPγS (guanosine 5'-O-[gamma-thio]triphosphate) autoradiography. STZ treatment was associated with mechanical allodynia and thermal hypoalgesia. Novel object recognition was unaltered in diabetic rats. STZ treatment was associated with impaired performance in the Morris water maze acquisition phase, but there were no differences in memory retrieval in the probe trial. Stimulus-response learning in the water maze cued trial was also disrupted in STZ-treated rats, possibly indicating sensorimotor deficits. CB1 receptor agonist-stimulated [(35)S]GTPγS binding was attenuated in the substantia nigra of STZ-treated rats but unaltered in the hippocampus. In conclusion, STZ treatment as a model of diabetic neuropathy was associated with specific functional deficits in the Morris water maze, effects which may be related to altered CB1 receptor functionality in the substantia nigra.
authors.affiliation: Pharmacology and Therapeutics, School of Medicine, Ireland; NCBES Neuroscience Centre, Ireland; Centre for Pain Research, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Moriarty
authors.affiliation: Pharmacology and Therapeutics, School of Medicine, Ireland; NCBES Neuroscience Centre, Ireland; Centre for Pain Research, Ireland.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lang
authors.affiliation: Department of Opthalmology, Galway University Hospital, Ireland.
authors.forename: Zubair
authors.initials: Z
authors.lastname: Idrees
authors.affiliation: School of Psychology, Ireland; NCBES Neuroscience Centre, Ireland; Centre for Pain Research, Ireland; Galway Diabetes Research Centre, National University of Ireland, Galway, Ireland.
authors.forename: Brian E
authors.initials: BE
authors.lastname: McGuire
authors.affiliation: Pharmacology and Therapeutics, School of Medicine, Ireland; NCBES Neuroscience Centre, Ireland; Centre for Pain Research, Ireland; Galway Diabetes Research Centre, National University of Ireland, Galway, Ireland. Electronic address: david.finn@nuigalway.ie.
authors.forename: David P
authors.initials: DP
authors.lastname: Finn
mesh_terms: D000818:Animals; D001345:Autoradiography; D003463:Cues; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000523:psychology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism; D059225:Nociception / Q000502:physiology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology; D065853:Spatial Learning / Q000502:physiology*; D013311:Streptozocin; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D043884:Receptor, Cannabinoid, CB1; D013311:Streptozocin
keywords: Cannabinoid(1) (CB(1)) receptor; Diabetes; Morris water maze; Neuropathic pain; Streptozotocin; [(35)S]GTPγS binding