Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task.
BACKGROUND
Atypical antipsychotics improve cognitive function, including working memory, in schizophrenia. Some atypical antipsychotics have been reported to activate the locus coeruleus and induce beta-adrenoceptor antagonist sensitive c-Fos-like immunoreactivity in the prefrontal cortex.


METHODS
The present study investigated the effects of chronic treatment of rats with risperidone (1 mg kg(-1) day(-1) s.c.), clozapine (10 mg kg(-1) day(-1) s.c.), or acidified saline vehicle control for 2, 4, or 8 weeks on spatial working memory performance in a delayed matching-to-place water maze task with a 60-s inter-trial retention interval with and without acute challenge with propranolol (10 mg/kg i.p.).


RESULTS
Treatment with risperidone for 8 weeks, but not 2 or 4 weeks, significantly improved working memory performance. In contrast, treatment with clozapine for up to 8 weeks did not improve working memory. Acute challenge with propranolol blocked the improvement in working memory produced by chronic treatment with risperidone, but had no significant effect on performance in saline- or clozapine-treated animals.


CONCLUSIONS
The delayed matching-to-place water maze task may prove valuable in the investigation of the behavioural pharmacology of the cognitive effects of antipsychotic drugs. These data suggest that beta adrenoceptors may contribute to the cognitive effects of chronic treatment with atypical antipsychotics.
Lim
Ee Peng
EP
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Building MD2, 18 Medical Drive, Singapore, 117597, Singapore. gavindawe@nus.edu.sg.
Verma
Vivek
V
Nagarajah
Rajini
R
Dawe
Gavin S
GS
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology*; D012559:Schizophrenia; D013028:Space Perception / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D014150:Antipsychotic Agents; D011433:Propranolol; D003024:Clozapine; D018967:Risperidone