Abstract
The neurotransmitter norepinephrine (NE) has been shown to modulate cerebellar-dependent learning and memory. Lesions of the nucleus locus coeruleus or systemic blockade of noradrenergic receptors has been shown to delay the acquisition of several cerebellar-dependent learning tasks. To date, no studies have shown a direct involvement of cerebellar noradrenergic activity nor localized the post-synaptic response to cerebellar beta-noradrenergic receptor signaling. Using ipsilateral, localized infusions into cerebellar lobule HVI and interpositus (IP), we have established that blocking beta-noradrenergic receptors with propranolol significantly impairs acquisition of conditioned responses. Furthermore, interrupting activation of cAMP-dependent PKA in the cerebellum using Rp-cAMPS completely prevents acquisition. However, neither blocking beta-adrenergic receptors nor blocking PKA activation significantly interferes with performance of established conditioned responses when administered after the learned response is formed.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic beta-Antagonists / administration & dosage
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Analysis of Variance
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Animals
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Cerebellum / cytology
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Cerebellum / drug effects
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Cerebellum / metabolism*
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Conditioning, Eyelid / drug effects
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Conditioning, Eyelid / physiology*
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Cyclic AMP / administration & dosage
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Cyclic AMP / analogs & derivatives*
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / physiology*
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Male
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Microinjections
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Neurons / drug effects
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Neurons / metabolism
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Norepinephrine / metabolism*
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Propranolol / administration & dosage
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Protein Kinase Inhibitors / administration & dosage
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Rats
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Rats, Inbred F344
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Reaction Time / drug effects
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Reaction Time / physiology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Thionucleotides / administration & dosage
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Time Perception / drug effects
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Time Perception / physiology
Substances
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Adrenergic beta-Antagonists
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Protein Kinase Inhibitors
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Thionucleotides
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adenosine-3',5'-cyclic phosphorothioate
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Propranolol
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Norepinephrine