Naloxone enhancement of memory

Messing, Rita B.; Jensen, Robert A.; Martinez, Joe L.; Spiehler, Vina; Vasquez, Beatriz J.; Soumireu-Mourat, Bernard; Liang, Keng Chen; McGaugh, James L.

doi:10.1016/s0163-1047(79)92328-8

Cited by 207 publications

(48 citation statements)

References 15 publications

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“…Enkephalins are part of the endogenous opioid system, which modulates many functions affected by AD, including learning and memory (Messing et al, 1979;Gallagher, 1982;Gallagher et al, 1983;Bodnar and Klein, 2005), synaptic plasticity (Derrick et al, 1992;Do et al, 2002), and emotional behaviors (Nieto et al, 2005). Preproenkephalin (Penk) is proteolytically cleaved to produce met-and leu-enkephalins in the regulated secretory pathway.…”

Section: Introductionmentioning

confidence: 99%

Enkephalin Elevations Contribute to Neuronal and Behavioral Impairments in a Transgenic Mouse Model of Alzheimer's Disease

Meilandt

Gui²,

Chin³

et al. 2008

J. Neurosci.

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The enkephalin signaling pathway regulates various neural functions and can be altered by neurodegenerative disorders. In Alzheimer's disease (AD), elevated enkephalin levels may reflect compensatory processes or contribute to cognitive impairments. To differentiate between these possibilities, we studied transgenic mice that express human amyloid precursor protein (hAPP) and amyloid-␤ (A␤) peptides in neurons and exhibit key aspects of AD. Met-enkephalin levels in neuronal projections from the entorhinal cortex and dentate gyrus (brain regions important for memory that are affected in early stages of AD) were increased in hAPP mice, as were preproenkephalin mRNA levels. Genetic manipulations that exacerbate or prevent excitotoxicity also exacerbated or prevented the enkephalin alterations. In human AD brains, enkephalin levels in the dentate gyrus were also increased. In hAPP mice, enkephalin elevations correlated with the extent of A␤-dependent neuronal and behavioral alterations, and memory deficits were reduced by irreversible blockade of -opioid receptors with the antagonist ␤-funaltrexamine. We conclude that enkephalin elevations may contribute to cognitive impairments in hAPP mice and possibly in humans with AD. The therapeutic potential of reducing enkephalin production or signaling merits further exploration.

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Section: Introductionmentioning

confidence: 99%

Enkephalin Elevations Contribute to Neuronal and Behavioral Impairments in a Transgenic Mouse Model of Alzheimer's Disease

Meilandt

Gui²,

Chin³

et al. 2008

J. Neurosci.

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“…For example, systemic administration of the nonselective opioid receptor antagonist naloxone facilitates the acquisition but impairs the extinction and overexpectation of learned fear (Fanselow and Bolles 1979;McNally and Westbrook 2003;McNally et al 2004a). Moreover, post-training injections of naloxone have been shown to enhance retention of an avoidance task (Messing et al 1979), and in infant rats pretest naloxone injections have been shown to alleviate infantile amnesia of a fear conditioning session (Weber et al 2006). Although a number of studies have demonstrated a role for the m-opioid receptor (MOR) in such effects (e.g., Fanselow et al 1991;McNally et al 2004b), a few studies have suggested that the k-opioid receptor (KOR) may also contribute to fear learning.…”

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confidence: 99%

Kappa opioid receptors mediate where fear is expressed following extinction training

Cole¹,

Richardson²,

McNally³

2011

Learn. Mem.

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Six experiments used a within-subjects renewal design to examine the involvement of kappa opioid receptors (KORs) in regulating the expression and recovery of extinguished fear. Rats were trained to fear a tone conditioned stimulus (CS) via pairings with foot shock in a distinctive context (A). This was followed by extinction training of the CS in a second context (B). Finally, all rats were tested for fear to the tone in the extinction context (ABB) and the training (ABA) or a novel (ABC) context. Intracerebroventricular (ICV) infusion of the KOR antagonist nor-binaltorphimine dihydrochloride (nor-BNI) dose-dependently prevented ABA renewal of fear, but had no effect on the expression of ABC renewal, the expression of extinction, or the expression of nonextinguished fear. Conversely, pretest infusion of the KOR agonist U50,488 hydrochloride (U50,488) selectively facilitated the expression of ABA renewal and had no effect on the expression of extinction. Pretest infusion of nor-BNI had no effect on the expression of context-specific latent inhibition. Collectively, these results suggest that KORs gate the expression of fear following extinction training and may comprise a critical neuropeptide component of the circuitry underlying context-dependent expression of fear.

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“…This potential worsening of retrograde amnesia appeared to be especially marked for memory of shape stimuli. The absence of beneficial effects of high dose naloxone on the measure of retrograde amnesia is particularly puzzling since the preclinical research demonstrating naloxone reduction or prevention of the amnestic effects of ECS primarily used retrograde memory paradigms (Messing et al 1979;Carrasco et al 1982). The absence of a beneficial effect of naloxone on the speed of orientation recovery was congruent with the findings regarding retrograde amnesia.…”

Section: Discussionmentioning

confidence: 67%

“…In rats, retrograde amnesia caused by ECS can be blocked by preventing the activation of a subset of cell bodies in the brain ␤ -endorphin system originating in the midbrain reticular formation and in the locus ceruleus (Izquierdo and Netto 1985). Of particular relevance are the findings that naloxone may reverse ECSinduced retrograde amnesia for a shuttle-avoidance task in rats (Messing et al 1979;Carrasco et al 1982). Naloxone may also reverse the retention deficits for learned avoidance associated with subconvulsive stimulation in the amygdala (Liang et al 1983) and impairment of spatial memory due to subconvulsive stimulation in the dentate gyrus (Collier and Routtenberg 1984).…”

mentioning

confidence: 99%

Naloxone in the Prevention of the Adverse Cognitive Effects of ECT A Within-Subject, Placebo Controlled Study

Prudic¹,

Fitzsimons

Nobler

et al. 1999

Neuropsychopharmacology

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Electroconvulsive therapy (ECT) is a highly effective treatment for major depression, but is also associated with characteristic cognitive side effects. Several reports document that endogenous opioids and their receptors are activated by electroconvulsive shock (ECS) and that naloxone in doses sufficient to block endogenous opioid receptors may reverse ECS-induced retrograde amnesia. This placebo-controlled, randomized, within-patient study was conducted to examine the potential of naloxone, given in doses sufficient to block opioid receptors (high dose)Electroconvulsive therapy (ECT) is a highly effective treatment for major depression and a variety of other disorders . However, the cognitive side effects of ECT are the major factor limiting its use. The cognitive consequences of ECT involve a period of postictal disorientation immediately following the induced seizure, as well as a pattern of more sustained neuropsychological deficits, principally anterograde and retrograde amnesia .There is substantial evidence that electroconvulsive shock (ECS) in experimental animals alters the concentrations of endogenous opioid peptides and the density of their receptors (Holaday et al. 1986). Opioids produce effects through at least three different receptors, , ␦ , and (Mansour et al. 1988; Quirion 1988). The receptors and ␦ have been extensively studied, and agonists at these receptors generally interfere with learning and memory, resulting in both anterograde and retrograde amnesia. The role of receptors in learning and memory is more complex. While agonists may impair memory in a dose-dependent fashion (Colombo et al., 1992), From they may also ameliorate memory deficits due to disruption of cholinergic transmission (Hiramatsu et al. 1996).Repeated ECS stimulates the release of proenkephalin and proopiomelanocortin ( ␤ -endorphin) (Tortella et al. 1989) and results in increased abundance of mRNA for preproenkepohalin in the hypothalmus and hippocampus (Yoshikawa et al. 1985;Xie et al. 1989;Simmons and Chavkin 1996). In the perforant pathway, projecting from entorhinal cortex to the hippocampal dentate gyrus, repeated ECS results in increased enkephalin immunostaining. In contrast, the release of dynorphin appears to be more complex. While increased dynorphin immunostaining has been found in limbic and basal ganglia structures, chronic ECS results in decreased levels in the mossy fiber axons of the dentate granule cells (Kanamatsu et al. 1986;Lasön et al. 1992). Overall, it appears that repeated ECS results in widespread increased synthesis and release in the proenkephalin system, and large decreases in the prodynorphin system in the hippocampus. Increased peptide synthesis and release may account for some findings of a sustained decreased density of and ␦ receptors following chronic ECS (Nakata et al. 1985;Crain et al. 1987). In humans, ECT has been found to result acutely in large increases in plasma ␤ -endorphin immunoreactivity (Alexopoulos et al. 1983;Weizman et al. 1987;Young et al. 1991).In a number of models...

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Naloxone enhancement of memory

Cited by 207 publications

References 15 publications

Enkephalin Elevations Contribute to Neuronal and Behavioral Impairments in a Transgenic Mouse Model of Alzheimer's Disease

Enkephalin Elevations Contribute to Neuronal and Behavioral Impairments in a Transgenic Mouse Model of Alzheimer's Disease

Kappa opioid receptors mediate where fear is expressed following extinction training

Naloxone in the Prevention of the Adverse Cognitive Effects of ECT A Within-Subject, Placebo Controlled Study

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