Galantamine and donepezil differently affect isolation rearing-induced deficits of prepulse inhibition in mice.

Abstract

RATIONALE:

Previous studies have shown that alterations in acetylcholine (ACh) receptor subtypes might contribute to cognitive impairment observed in schizophrenia and that choline acetyltransferase activity in the parietal cortex is negatively correlated with the severity of such cognitive impairment. However, clinical data suggest that the acetylcholinesterase (AChE) inhibitors galantamine and donepezil have different effects on negative and cognitive symptoms in schizophrenia. Prepulse inhibition (PPI) deficits--sensory information-processing deficits observed in schizophrenia--may be useful models for studying the efficacy of AChE inhibitors as cognitive enhancers.

OBJECTIVES:

The present study examined the effects of galantamine and donepezil on PPI deficits induced by an environmental factor and drugs.

MATERIALS AND METHODS:

In the isolation-rearing model, 3-week-old male ddY mice were housed either in groups of five or six per cage or isolated in cages of the same size for more than 6 weeks. In the drug-induced model, apomorphine 1 mg/kg and MK-801 0.2 mg/kg were administered to 9- to 10-week-old male ddY mice.

RESULTS:

In isolation-reared mice, galantamine attenuated PPI deficits, while donepezil did not. Galantamine and donepezil both attenuated PPI deficits induced by apomorphine, but not by MK-801. The galantamine-induced improvements in PPI deficits were not prevented by the nicotinic ACh receptor antagonists mecamylamine and methyllycaconitine.

CONCLUSIONS:

These observations suggest that galantamine and donepezil have different effects on the environmentally induced PPI deficits and that these observations may be relevant to the different effects of these drugs observed clinically in schizophrenia.

• Authors: Ken Koda, Yukio Ago, Toshiyuki Kawasaki, Hitoshi Hashimoto, Akemichi Baba, Toshio Matsuda
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 196 Issue 2 Pg. 293-301 (Feb 2008) ISSN: 0033-3158 [Print] Germany
• PMID: 17912499 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholinesterase Inhibitors
• Chrna7 protein, mouse
• Indans
• Nicotinic Antagonists
• Piperidines
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor
• Galantamine
• methyllycaconitine
• Mecamylamine
• Dizocilpine Maleate
• Donepezil
• Risperidone
• Apomorphine
• Aconitine

Topics

• Aconitine (analogs & derivatives, pharmacology)
• Acoustic Stimulation
• Analysis of Variance
• Animals
• Animals, Outbred Strains
• Apomorphine (pharmacology)
• Behavior, Animal (drug effects, physiology)
• Cholinesterase Inhibitors (pharmacology)
• Dizocilpine Maleate (pharmacology)
• Donepezil
• Dose-Response Relationship, Drug
• Galantamine (pharmacology)
• Indans (pharmacology)
• Male
• Mecamylamine (pharmacology)
• Mice
• Neural Inhibition (drug effects, physiology)
• Nicotinic Antagonists (pharmacology)
• Piperidines (pharmacology)
• Receptors, Nicotinic (physiology)
• Reflex, Startle (drug effects)
• Risperidone (pharmacology)
• Social Isolation (psychology)
• alpha7 Nicotinic Acetylcholine Receptor