Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 11, Issue 6, Pages 845-850Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1461145708008730
Keywords
antipsychotic drugs; conditioned avoidance response; donepezil; galantamine; schizophrenia
Funding
- Swedish Research Council [4747]
- Karolinska Institutet
- Magnus Bergvall Foundation
- Fredrik and Ingrid Thuring Foundation
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Acetylcholine (ACh) esterase inhibitors like galantamine and donepezil have been tested as adjunct treatment in schizophrenia. Although ACh esterase inhibition might confer some antipsychotic activity, the role of allosteric potentiation of nicotinic ACh receptors (nAChRs), which is an additional mechanism of galantamine, remains elusive. Therefore, the potential antipsychotic-like effects of galantamine and donepezil, respectively, alone, and in combination with the dopamine D(2/3) receptor antagonist, raclopride, were tested in the conditioned avoidance response (CAR) test and extrapyramidal side-effect liability was assessed with the catalepsy test. Neither galantamine nor donepezil alone suppressed CAR selectively. Galantamine, but not donepezil, enhanced the raclopride-induced suppression of CAR, predicting augmentation of antipsychotic activity. In contrast to donepezil, galantamine did not increase catalepsy, alone or combined with raclopride. These data Suggest that allosteric potentiation of nAChRs may mediate the antipsychotic-like effect of adjunctive galantamine and provide support for the development of alpha(7) nAChR-selective allosteric potentiators for schizophrenia.
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