Acetylcholine efflux from retrosplenial areas and hippocampal sectors during maze exploration

Anzalone, Steven; Roland, Jessica J.; Vogt, Brent A.; Savage, Lisa M.

doi:10.1016/j.bbr.2009.02.023

Cited by 21 publications

(21 citation statements)

References 80 publications

(130 reference statements)

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“…This assumption aligns with the well-established role of the cholinergic system in learning and memory processes (for review see Hasselmo, 2006), and the notion that pharmacological agents producing increase in the acetylcholine release (Sullivan, 2000) and/ or synthesis (Friedman et al, 1976) can improve cognitive performance (Iversen, 1997). Of relevance to this study, it was shown earlier that acetylcholine levels in the brain correlate with spatial memory and recognition performance (Tang and Aigner, 1996;Anzalone et al, 2009) and that the treatment with CB1R antagonists increases the acetylcholine release in the medial prefrontal cortex and hippocampus of rodents (Gessa et al, 1998;Tzavara et al, 2003Tzavara et al, , 2008Degroot et al, 2006). Moreover, electrically evoked acetylcholine release is significantly increased in hippocampal slices from CB1R-deficient mice .…”

Section: Discussionsupporting

confidence: 64%

MK-7128, a novel CB1 receptor inverse agonist, improves scopolamine-induced learning and memory deficits in mice

Dillon

Lubbers²,

Ferguson³

et al. 2011

Behavioural Pharmacology

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Cannabinoid receptors (CBRs) play an important role in a variety of physiological functions and have been considered drug targets for obesity and psychiatric disorders. In particular, the CB1R is highly expressed in brain regions crucial to learning and memory processes, and several lines of evidence indicate that pharmacological blockade of this receptor could have therapeutic applications in the treatment of cognitive disorders. In this study, we investigated whether MK-7128 (0.1, 0.3, and 1 mg/kg, orally), a novel and selective CB1R inverse agonist, could improve learning and memory deficits induced by scopolamine (1 mg/kg, subcutaneously) in mice. The investigators also assessed CB1R occupancy in the brain to ensure target engagement of MK-7128, and showed that MK-7128 significantly improved both Y-maze spontaneous alternation and object habituation performance in scopolamine-treated mice and inhibits the binding of radioiodinated AM251 in murine cortex and hippocampus. These data indicate that MK-7128 improves cognitive performance in a model of cholinergic hypofunction and suggest that efficacy is achieved at relatively low levels of CB1R occupancy in the brain. Our results extend earlier findings suggesting a role of CB1Rs in the modulation of memory processes and a potential therapeutic application for CB1R inverse agonists in cognitive disorders.

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Section: Discussionsupporting

confidence: 64%

MK-7128, a novel CB1 receptor inverse agonist, improves scopolamine-induced learning and memory deficits in mice

Dillon

Lubbers²,

Ferguson³

et al. 2011

Behavioural Pharmacology

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“…This reduction in basal forebrain cholinergic cell numbers is hypothesized to be a result of EtOH’s effects on neuroimmune activation that can lead to neural degeneration via oxidative stress or excitotoxicity (Crews et al, 2015). Interestingly, the decrease in cholinergic cell population within the MS/DB following AIE did not significantly alter ACh efflux within the hippocampus or impair spontaneous alternation and Barnes maze behaviors, which are ACh-dependent (Lalonde, 2002; Seeger et al, 2004; Anzalone et al, 2009). It is important to note that AIE only produces a decrease in the ChAT+/ nestin− population in the MS/DB.…”

Section: Discussionmentioning

confidence: 90%

Adolescent binge ethanol exposure alters specific forebrain cholinergic cell populations and leads to selective functional deficits in the prefrontal cortex

Fernandez

Savage

2017

Neuroscience

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Adolescence has been identified as a vulnerable developmental time period during which exposure to drugs can have long-lasting, detrimental effects. Although adolescent binge-like ethanol (EtOH) exposure leads to a significant reduction of forebrain cholinergic neurons, EtOH’s functional effect on acetylcholine (ACh) release during behavior has yet to be examined. Using an adolescent intermittent ethanol exposure model (AIE), rats were exposed to binge-like levels of EtOH from postnatal day (PD) 25–55. Three weeks following the final EtOH exposure, cholinergic functioning was assessed during a spontaneous alternation protocol. During maze testing, ACh levels increased in both the hippocampus and prefrontal cortex. However, selectively in the prefrontal cortex, AIE rats displayed reduced levels of behaviorally-relevant ACh efflux. We found no treatment differences in spatial exploration, spatial learning, spatial reversal, or novel object recognition. In contrast, AIE rats were impaired during the first attentional set shift on an operant set-shifting task, indicative of an EtOH-mediated deficit in cognitive flexibility. A unique pattern of cholinergic cell loss was observed in the basal forebrain following AIE: Within the medial septum/diagonal band there was a selective loss (30%) of choline acetyltransferase (ChAT) positive neurons that were nestin negative (ChAT+/ nestin−); whereas in the Nucleus basalis of Meynert (NbM) there was a selective reduction (50%) in ChAT+/ nestin+. These results indicate that early adolescent binge EtOH exposure leads to a long-lasting frontocortical functional cholinergic deficit, driven by a loss of ChAT+/ nestin+ neurons in the NbM, which was associated with impaired cognitive flexibility during adulthood.

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“…Methods for cannula implantation were as previously described (Savage et al. , 2003; Roland & Savage, 2007; Anzalone et al. , 2009).…”

Section: Methodsmentioning

confidence: 99%

Cortical cholinergic abnormalities contribute to the amnesic state induced by pyrithiamine‐induced thiamine deficiency in the rat

Anzalone¹,

Vetreno²,

Ramos³

et al. 2010

Eur J of Neuroscience

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Although the key neuropathology associated with diencephalic amnesia are lesions to the thalamus and/or mammillary bodies, functional deactivation of the hippocampus and associated cortical regions also appear to contribute to the memory dysfunction. For example, there is loss of forebrain cholinergic neurons and alterations in stimulated acetylcholine (ACh) levels in hippocampus and cortex in animal models of diencephalic amnesia associated with thiamine deficiency. In the present study, the pyrithiamine-induced thiamine deficiency (PTD) rat model was used to assess the functional relationships between thalamic pathology, behavioral impairment, ACh efflux and cholinergic innervation of the hippocampus and cortex. In PTD-treated rats, ACh efflux during behavioral testing was blunted to differing degrees in the hippocampus, medial frontal cortex and the retrospenial cortex. In addition, significant reductions in cholinergic fiber densities were observed in each of those regions. However, only hippocampal cholinergic fiber density correlated significantly with ACh efflux in the same region suggesting that the reduction in cortical ACh efflux in cases of diencephalic amnesia cannot be fully explained by a loss of cholinergic fiber innervation. This notion supports the emerging theory that the functional consequences of the distal effects of lesions go beyond simple deafferentation. Specifically, some frontal cortical regions exhibit hypersensitivity to deafferentation that is only detected during behavioral and/or physiological demand.

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Acetylcholine efflux from retrosplenial areas and hippocampal sectors during maze exploration

Cited by 21 publications

References 80 publications

MK-7128, a novel CB1 receptor inverse agonist, improves scopolamine-induced learning and memory deficits in mice

MK-7128, a novel CB1 receptor inverse agonist, improves scopolamine-induced learning and memory deficits in mice

Adolescent binge ethanol exposure alters specific forebrain cholinergic cell populations and leads to selective functional deficits in the prefrontal cortex

Cortical cholinergic abnormalities contribute to the amnesic state induced by pyrithiamine‐induced thiamine deficiency in the rat

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