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.

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

“…Moreover Zoja et al observed that in kidney biopsies from patients with diabetic nephropathy, CB2 is down-regulated, and moreover, its deletion worsens the kidney state, confirming the receptor protective action [129]. Moriarty et al observed that STZ-diabetic rats show an alteration in CB1 receptor functionality in the substantia nigra, which may be associated with diabetes and diabetic neuropathic pain [133]. Surely all of this evidence needs further investigation, but new perspectives for the management of this complex degenerative disease are surely emerging.…”

Effect of pregabalin on contextual memory deficits and inflammatory state-related protein expression in streptozotocin-induced diabetic mice

“…The duration of diabetes mellitus is thought to be one of the key factors for rodent studies on DNP and its effective treatment (Obrosova 2009 ), as well as diabetes-related cognitive deficits (Biessels and Gispen 2005 ). This is due to the fact that both these diabetes-related complications share a common etiology, i.e., neuropathy (Moriarty et al 2016 ). Since the main objective of the present research was to assess the impact of pregabalin on learning and memory in conditions related to DNP, this study was performed 3 weeks after STZ injection.…”

“…Studies on the cognitive abilities of STZ-treated diabetic rodents are based on several learning tasks (Biessels et al 2002 ; Moriarty et al 2016 ). To assess the effect of pregabalin on learning and memory in diabetic mice, we used a passive avoidance task.…”

Development of CGRP-dependent pain and headache related behaviours in a rat model of concussion: Implications for mechanisms of post-traumatic headache

“…The novel object recognition test is designed to evaluate deficits in recognition memory in rodents, as a measure of the severity of the brain injury. The procedure used for the novelobject recognition test was similar to that described previously (26,27), with some modifications. The apparatus consisted of a Perspex arena (45 cm 2 ).…”