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Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat
- Source :
- Psychopharmacology. 202(1-3)
- Publication Year :
- 2008
-
Abstract
- Positive allosteric modulators of the glutamatergic α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor do not stimulate AMPA receptors directly but delay deactivation of the receptor and/or slow its desensitisation. This results in increased synaptic responses and enhanced long-term potentiation. Thus, it has been suggested that such compounds may have utility for the treatment of cognitive impairment. The objective of the study was to investigate the effect of an AMPA positive modulator, CX691, (1) in three rodent models of learning and memory, (2) on neurochemistry in the dorsal hippocampus and medial prefrontal cortex following acute administration, and (3) on brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in the rat hippocampus following acute and sub-chronic administration. CX691 attenuated a scopolamine-induced impairment of cued fear conditioning following acute administration (0.1 mg/kg p.o.) and a temporally induced deficit in novel object recognition following both acute (0.1 and 1.0 mg/kg p.o.) and sub-chronic (bi-daily for 7 days) administration (0.01, 0.03, 0.1 mg/kg p.o.). It also improved attentional set-shifting following sub-chronic administration (0.3 mg/kg p.o.). Acute CX691 (0.1, 0.3 and 1.0 mg/kg, p.o.) increased extracellular levels of acetylcholine in the dorsal hippocampus and medial prefrontal cortex and dopamine in the medial prefrontal cortex. Sub-chronic administration of CX691 (0.1 mg/kg, p.o.) elevated BDNF mRNA expression in both the whole and CA1 sub-region of the hippocampus (P
- Subjects :
- Male
medicine.medical_specialty
Dopamine
Scopolamine
Hippocampus
Prefrontal Cortex
AMPA receptor
Muscarinic Antagonists
Norepinephrine
Cognition
Piperidines
Neurotrophic factors
Internal medicine
medicine
Animals
Attention
Fear conditioning
RNA, Messenger
Receptors, AMPA
Receptor
Prefrontal cortex
In Situ Hybridization
Nootropic Agents
Pharmacology
Oxadiazoles
Brain-Derived Neurotrophic Factor
Long-term potentiation
Recognition, Psychology
Fear
Amygdala
Acetylcholine
Rats
Endocrinology
Conditioning, Operant
Cues
Psychology
Neuroscience
medicine.drug
Subjects
Details
- ISSN :
- 14322072
- Volume :
- 202
- Issue :
- 1-3
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....090a6ce3b9a9a4383db03e6d874e0f45