Nicotinic modulation in an animal model of a form of associative learning impaired in Alzheimer's disease.

Woodruff-Pak DS, Santos IS.

Department of Psychology, 
Temple University,
Philadelphia, PA 19122


Eyeblink classical conditioning is a widely used associative learning paradigm that has striking behavioral and neurobiological parallels between humans and other mammals. Eyeblink conditioning is impaired in older organisms, and patients with Alzheimer's disease (AD) are impaired beyond the normal aging deficit.  The cholinergic system is of demonstrated involvement in eyeblink conditioning.  Blockade of nicotinic cholinergic receptors with mecamylamine prolonged acquisition of conditioned responses (CRs) in young adult rabbits, and the nicotinic agonist, GTS-21 ameliorated conditioning deficits in older rabbits. Galantamine induces allosteric modulation of nicotinic cholinergic receptors to increase acetylcholine release as well as acting as an acetylcholinesterase inhibitor.  Galantamine doses of 0.0, 1.0, 2.0, 3.0, and 4.0 mg/kg were tested in ten daily sessions in 40 retired breeder rabbits (mean age = 29 months) in the 750 ms delay conditioning paradigm. A dose of 3 mg/kg galantamine was effective in improving conditioning in older rabbits, enabling them to achieve learning criterion rapidly and to produce a very high percentage of CRs.  Control tests of rabbits in explicitly unpaired conditions demonstrated that non-associative factors could not account for the results. The efficacy of galantamine in a learning paradigm that shows severe impairment in AD indicates that the drug may be effective as a cognition-enhancer in AD.

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Research abstracts
  Galantamine: its use in Alzheimer's
  Galantamine: in Alzheimer's patients
acetylcholinesterase inhibition
  Galantamine: therapeutic effects beyond cognition
  Galantamine: benefits to Alzheimer's patients
nicotinic receptors in Alzheimer's
  Galantamine: a study in Alzheimer's  
  Galantamine: its effects on Alzheimer's  
  Galantamine: a new treatment for Alzheimer's
  Galantamine: effect on nicotinic receptor binding
  Galantamine: an allosterically potentiating ligand
  Galantamine: nicotinic modulation in an animal model
  Galantamine: memory & nicotinic receptors in rats  
  Galantamine: a 6 month study: