title: Analysis of mechanisms for memory enhancement using novel and potent 5-HT1A receptor ligands.
abstract: In light of the involvement of serotonergic 5-HT1A receptors in the mediation of the memory of aversive events, the potent and selective 5-HT1A receptor antagonists, MC18 fumarate and VP08/34 fumarate, were tested in the passive avoidance task (PA), a rodent model of instrumental conditioning. Either alone or in combination with the prototypical agonist 8-OH-DPAT, MC18 fumarate at doses (0.1, 0.3 and 1mg/kg given 15min prior to training) exerted a dose-dependent facilitation of PA memory retention. When administered 15min prior to 8-OH-DPAT (0.3 and 1mg/kg), MC18 fumarate at a dose of 0.3mg/kg, enhanced significantly the impairment of PA retention caused by 8-OH-DPAT (1mg/kg). However, VP08/34 fumarate given at the same doses exerted no statistically effect on PA retention memory. Furthermore, VP08/34 fumarate given 15min prior to 8-OH-DPAT (0.3 and 1mg/kg) only slightly enhanced the PA impairment induced by 8-OH-DPAT. In conclusion, the profile of MC18 fumarate is intriguing since it behaves in a manner which differs from both full receptor antagonists such as NAD-299 or partial receptor agonists. The results also illustrate the importance of subtle receptor interaction and probably ligand efficacy in determining the actions of two almost identical 5-HT1A receptor ligands in cognitive function such as instrumental learning.
authors.affiliation: Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. Electronic address: vpittala@unict.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pittalà
authors.affiliation: Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Siracusa
authors.affiliation: Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Salerno
authors.affiliation: Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
authors.affiliation: Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Modica
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, SE-171 77 Stockholm, Sweden.
authors.forename: Nather
authors.initials: N
authors.lastname: Madjid
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, SE-171 77 Stockholm, Sweden. Electronic address: Sven.Ove.Ogren@ki.se.
authors.forename: Sven Ove
authors.initials: SO
authors.lastname: Ogren
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005650:Fumarates / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001578:Benzopyrans; D005650:Fumarates; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C108607:robalzotan
keywords: 5-HT(1A) receptors; 8-OH-DPAT; Learning and memory; MC18; Passive avoidance