title: Modulatory effects of two novel agonists for serotonin receptor 7 on emotion, motivation and circadian rhythm profiles in mice.
abstract: Serotonin receptor 7, i.e. 5-HT(7) protein coded by Htr7 gene, was discovered in supra-chiasmatic nucleus (SCN) of the hypothalamus but is widespread in the forebrain. Studies have shown that this receptor is involved in learning/memory, regulation of mood and circadian rhythms. The modulatory effects of two novel agonists, LP-211 and LP-378, were assessed in male adult CD-1 mice with a battery of behavioral tests. Exp. 1 (Black/White Boxes, BWB: Adriani et al., 2009) and Exp. 2 (Dark/Light, D/L; Novelty-seeking, N-S) show: a) that LP-211 administration (acutely, at a 0.25 mg/kg dose i.p.) increases locomotion and BWB exploration; b) that the time spent away from an aversive, lit chamber (i.e., stress-induced anxiety) and in a new environment (i.e., novelty-induced curiosity) are both reduced. Sub-chronic LP-211 (at a 2.5 mg/kg dose i.p.) reveals a sensitization of locomotor-stimulant properties over 4-5 days. In Exp. 3 (BWB), a three- to four-fold dosage (acutely, at 0.83 mg/kg i.p.) is needed with LP-378 to increase locomotion and BWB exploration. In Exp. 4, mice under constant-light conditions reveal the expected spontaneous lengthening (1.5 h per day) of circadian rhythms. A significant phase advance is induced by LP-211 (at a 0.25 mg/kg dose i.p., administered around activity offset), with onset of activity taking place 6 h earlier than in controls. In summary, LP-211 is able to act consistently onto exploratory motivation, anxiety-related profiles, and spontaneous circadian rhythm. In the next future, agonist modulation of 5-HT(7) receptors might turn out to be beneficial for sleep and/or anxiety disorders. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors.affiliation: Behavioral Neuroscience Section, Dept. of Cell Biology & Neurosciences, Istituto Superiore di Sanità, viale Regina Elena 299, I-00161 Rome, Italy. walter.adriani@iss.it
authors.forename: Walter
authors.initials: W
authors.lastname: Adriani
authors.forename: Domenica
authors.initials: D
authors.lastname: Travaglini
authors.forename: Enza
authors.initials: E
authors.lastname: Lacivita
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects*; D004644:Emotions / Q000187:drug effects*; D008297:Male; D051379:Mice; D009042:Motivation / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: C573815:N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor