Acquisition, retention, and recall of memory after injection of RS67333, a 5-HT(4) receptor agonist, into the nucleus basalis magnocellularis of the rat.
The serotonin 5-HT4 subtype receptor is predominantly localized into anatomical structures linked to memory and cognition. A few experimental studies report that the acute systemic administration of selective 5-HT4 agonists has ameliorative effects on memory performance, and that these effects are reversed by contemporary administration of 5-HT4 receptor antagonists. To verify whether this procognitive action occurs via the activation of the cholinergic nucleus basalis magnocellularis (NBM)-cortical pathways, we examined the effects of RS67333, a selective partial agonist of the 5-HT4 receptor, on rat performance in a place recognition task upon local administration of the drug into the NBM area. The intra-NBM administration of RS67333 enhances the acquisition (200-500 ng/0.5 microL) and the consolidation (40-200 ng/0.5 microL) of the place recognition memory. These effects are reversed by pretreatment with the selective 5-HT4 receptor antagonist RS39604 (300 ng/0.5 microL). Conversely, the recall of memory is not affected by the 5-HT4 agonist. Our results indicate that 5-HT4 receptors located within the NBM may play a role in spatial memory and that the procognitive effect of RS67333 is due, at least in part, to the potentiation of the activity of cholinergic NBM-cortical pathways.
Orsetti
Marco
M
Dipartimento di Scienze C. A. F. e Farmacologiche, Università del Piemonte Orientale, 28100 Novara, Italy. orsetti@pharm.unipmn.it
Dellarole
Anna
A
Ferri
Simona
S
Ghi
Piera
P
D000109:Acetylcholine / Q000502:physiology; D000814:Aniline Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000502:physiology*; D007267:Injections; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology*; D012153:Retention, Psychology / Q000187:drug effects* / Q000502:physiology; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013028:Space Perception / Q000187:drug effects
D000814:Aniline Compounds; D010880:Piperidines; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C107826:RS 67333; D000109:Acetylcholine