Effects of 4-aminopyridine on classical conditioning of the rabbit (Oryctolagus cuniculus) nictitating membrane response

Wang, Desheng; Darwish, Deya S.; Schreurs, Bernard G.

doi:10.1097/01.fbp.0000224381.56121.15

Cited by 5 publications

(4 citation statements)

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“…Given the low but still significantly higher level of NMRs to the tone during habituation, it is possible that there may have been a nonassociative effect of copper when added to the drinking water. There is some precedent for other compounds having nonassociative effects on the rabbit NMR including 4-aminopyridine that was found to increase sensitivity to tone and air puff (Wang, Darwish, & Schreurs, 2006) and a serotonin antagonist that was found to reduce sensitivity to air puff (Welsh, Romano, & Harvey, 1998). The only animal model of altered copper levels in the brain is the Long-Evans Cinnamon rat that shares many of the pathological and biological characteristics of Wilson's disease, a genetic disorder of copper metabolism in which copper accumulates in the body.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol enhances classical conditioning of the rabbit heart rate response

Schreurs

Smith-Bell

Darwish

et al. 2007

Behavioural Brain Research

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The cholesterol-fed rabbit is a model of atherosclerosis and has been proposed as an animal model of Alzheimer's disease. Feeding rabbits cholesterol has been shown to increase the number of beta amyloid immunoreactive neurons in the cortex. Addition of copper to the drinking water of cholesterol-fed rabbits can increase this number still further and may lead to plaque-like structures. Classical conditioning of the nictitating membrane response in cholesterol-fed rabbits is retarded in the presence of these plaque-like structures but may be facilitated in their absence. In a factorial design, rabbits fed 2% cholesterol or a normal diet (0% cholesterol) for 8 weeks with or without copper added to the drinking water were given trace classical conditioning using a tone and periorbital electrodermal stimulation to study the effects of cholesterol and copper on classical conditioning of heart rate and the nictitating membrane response. Cholesterol-fed rabbits showed significant facilitation of heart rate conditioning and conditioning-specific modification of heart rate relative to normal diet controls. Consistent with previous research, cholesterol had minimal effects on classical conditioning of the nictitating membrane response when periorbital electrodermal stimulation was used as the unconditioned stimulus. Immunohistochemical analysis showed a significant increase in the number of beta amyloid positive neurons in the cortex, hippocampus and amygdala of the cholesterol-fed rabbits. Supplementation of drinking water with copper increased the number of beta amyloid positive neurons in the cortex of cholesterol-fed rabbits but did not produce plaque-like structures or have a significant effect on heart rate conditioning. The data provide additional support for our finding that, in the absence of plaques, dietary cholesterol may facilitate learning and memory. Cholesterol enhances rabbit heart rate conditioningThe cholesterol-fed rabbit has been used as an animal model of atherosclerosis since 1913 when Anitchkow first demonstrated that a cholesterol diet induced vascular lesions (Bocan, 1998;Fan & Watanabe, 2000;Finking & Hanke, 1997;Moghadasian, 2002). More recently, the cholesterol-fed rabbit has been proposed as an animal model of Alzheimer's disease (Ghribi, Larsen, Schrag, & Herman, 2006;Sjogren, Mielke, Gustafson, Zandi, & Skoog, 2006 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Sparks, 1997;Sparks, Martin, Gross, & Hunsaker III, 2000;Zatta, Zambenedetti, Stella, & Licastro, 2002). Based on the observation that patients with heart disease had beta amyloid st...

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Section: Discussionmentioning

confidence: 99%

Cholesterol enhances classical conditioning of the rabbit heart rate response

Schreurs

Smith-Bell

Darwish

et al. 2007

Behavioural Brain Research

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“…Since its first description (Schreurs et al, 1995), a number of the behavioral laws of CRM have been established (Buck, Seager, & Schreurs, 2001; Schreurs, Gonzales-Joekes, & Smith-Bell, 2006; Schreurs, Shi, Pineda, & Buck, 2000; Seager, Smith-Bell, & Schreurs, 2003), and investigation into its neural substrates has begun (Burhans & Schreurs, 2008). In addition, CRM is used routinely as a method of assessing the effects of drugs and diet manipulations on classical conditioning of the rabbit NMR (Schreurs, Smith-Bell, Lochhead, & Sparks, 2003; Wang, Darwish, & Schreurs, 2006). More recently, CRM has also been documented in a completely different response system, rabbit heart rate (Schreurs, Crum, Wang, & Smith-Bell, 2005; Schreurs et al, 2007).…”

Section: Conditioning-specific Reflex Modification (Crm)mentioning

confidence: 99%

Conditioning-specific reflex modification of the rabbit's nictitating membrane response and heart rate: Behavioral rules, neural substrates, and potential applications to posttraumatic stress disorder.

Burhans

Smith-Bell

Schreurs

2008

Behavioral Neuroscience

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Interest in classical conditioning is usually focused on anticipatory responses to a stimulus associated with a significant event, and it is assumed that responses to the event itself are reflexive, involuntary, and relatively invariant. However, there is compelling evidence that both the rabbit nictitating membrane response (NMR) and heart rate response (HR), well-known reflexive reactions to aversive events, can change quite dramatically as a function of learning when measured in the absence of the conditioned stimulus. In the case of NMR conditioning, a simple blink is transformed into a larger and more complex response. For HR conditioning, reflexive heart rate acceleration can actually change to heart rate deceleration. In both cases, the reflex comes to resemble the conditioned response and follows some of the same behavioral laws. This change in response to the aversive event itself or weaker forms of that event is called conditioning-specific reflex modification (CRM). CRM may force us to reevaluate the behavioral and neural consequences of classical conditioning and may have important consequences for the treatment of conditions such as posttraumatic stress disorder.

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“…By using radioactive in situ hybridization, a decrease has been shown in Kv1.1 α-subunit mRNA in the dorsal hippocampus at different stages of an odor-discrimination associative task in rats (Kourrich, Mourre, & Soumireu-Mourat, 2001). Finally, 4-AP (4-aminopyridine), a transient K + -channel blocker, improved classical conditioning responses in rabbits in normal (Wang, Darwish, & Schreurs, 2006) and pathological situations (Yokel, Allen, & Meyer, 1994). Taken together, the above-mentioned data support the suggestion that T-588 can act on K + channels to enhance learning responses for classically conditioned motor responses.…”

Section: Discussionmentioning

confidence: 99%

The cognitive enhancer T-588 partially compensates the motor associative learning impairments induced by scopolamine injection in mice.

Eleore

López-Ramos

et al. 2007

Behavioral Neuroscience

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The authors studied the effects of T-588 on scopolamine-induced memory impairments in the acquisition of a classical eyeblink conditioning in behaving adult mice. Mice injected with 0.3 mg/kg of scopolamine showed a marked deficit, compared with nontreated mice, in the acquisition of classical eyeblink conditioning using a trace paradigm. Coadministration of T-588 (0.05% wt/vol, in water) with scopolamine (0.3 mg/kg) significantly prevented this deficit in associative learning. To further assess the effects of T-588 on motor coordination and the cognitive deficits induced by scopolamine, the authors compared adult controls or scopolamine-treated mice in different behavioral tasks: rotarod, object recognition, passive avoidance, and prepulse inhibition. In all of these tasks, the authors found a significant impairment in the motor or cognitive abilities in scopolamine-injected mice, compared with controls. In addition, the coadministration of T-588 with scopolamine restored deficits induced by scopolamine alone. Importantly, the administration of T-588 alone did not evoke any change compared with values obtained for controls. These results suggest that T-588 could be used as a pharmacological agent to improve motor and associative learning disorders.

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Effects of 4-aminopyridine on classical conditioning of the rabbit (Oryctolagus cuniculus) nictitating membrane response

Cited by 5 publications

References 68 publications

Cholesterol enhances classical conditioning of the rabbit heart rate response

Cholesterol enhances classical conditioning of the rabbit heart rate response

Conditioning-specific reflex modification of the rabbit's nictitating membrane response and heart rate: Behavioral rules, neural substrates, and potential applications to posttraumatic stress disorder.

The cognitive enhancer T-588 partially compensates the motor associative learning impairments induced by scopolamine injection in mice.

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