Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders.
Cholinergic dysfunction has been shown to be central to the pathophysiology of Alzheimer's disease and has also been postulated to contribute to cognitive dysfunction observed in various psychiatric disorders, including schizophrenia. Deficits are found across a number of cognitive domains and in spite of several attempts to develop new therapies, these remain an unmet clinical need. In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female Hooded Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6h inter-trial interval (ITI). In all treatment groups, there was no preference for the left or right identical objects in the acquisition trial. Risperidone failed to enhance recognition memory in this paradigm whereas donepezil was effective such that rats discriminated between the novel and familiar object in the retention trial following a 6h ITI. Although a narrow dose range of PNU-282987 and RJR-2403 was tested, only one dose of each increased recognition memory, the highest dose of PNU-282987 (10mg/kg) and the lowest dose of RJR-2403 (0.1mg/kg), indicative of enhanced cognitive performance. Interestingly, these compounds were also efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory.
Bradford School of Pharmacy, University of Bradford, Richmond Road, BD7 1DP, UK.
Samantha L
SL
McLean
Manchester Pharmacy School, University of Manchester, Oxford Rd, M13 9PT, UK. Electronic address: b.grayson@manchester.ac.uk.
Ben
B
Grayson
Manchester Pharmacy School, University of Manchester, Oxford Rd, M13 9PT, UK.
Samuel
S
Marsh
Institute for Life Sciences, University of Southampton, University Road, SO17 1BJ, UK.
Samah H O
SH
Zarroug
Manchester Pharmacy School, University of Manchester, Oxford Rd, M13 9PT, UK.
Michael K
MK
Harte
Manchester Pharmacy School, University of Manchester, Oxford Rd, M13 9PT, UK.
Jo C
JC
Neill
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007189:Indans / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects*; D009538:Nicotine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects*; D012153:Retention, Psychology / Q000187:drug effects; D018967:Risperidone / Q000494:pharmacology
D014150:Antipsychotic Agents; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D002800:Cholinesterase Inhibitors; D007189:Indans; D018722:Nicotinic Agonists; C498513:PNU-282987; D010880:Piperidines; C012419:metanicotine; D009538:Nicotine; D000077265:Donepezil; D018967:Risperidone
Delay-dependent deficits; Female rat; Object recognition memory; α4β2 Nicotinic receptors; α7 Nicotinic receptors