title: Lsamp⁻/⁻ mice display lower sensitivity to amphetamine and have elevated 5-HT turnover.
abstract: In mice, the limbic system-associated membrane protein (Lsamp) gene has been implicated in locomotion, anxiety, fear reaction, learning, social behaviour and adaptation. Human data links the LSAMP gene to several psychiatric disorders and completed suicide. Here, we investigated changes in major monoamine systems in mice lacking the Lsamp gene. First, the locomotor and rewarding effects of amphetamine were studied in Lsamp(-/-) mice and Lsamp(+/+) mice. Second, monoamine levels in major brain regions in response to saline and amphetamine injections were measured and, third, the expression levels of dopamine system-related genes in the brain were studied in these mice. Lsamp(-/-) mice displayed lower sensitivity to amphetamine in the motility box. Likewise, in the place preference test, the rewarding effect of amphetamine was absent in Lsamp(-/-) mice. In all brain regions studied, Lsamp(-/-) mice displayed lower serotonin (5-HT) baseline levels, but a greater 5-HT turnover rate, and amphetamine increased the level of 5-HT and lowered 5-HT turnover to a greater extent in Lsamp(-/-) mice. Finally, Lsamp(-/-) mice had lower level of dopamine transporter (DAT) mRNA in the mesencephalon. In conclusion, Lsamp-deficiency leads to increased endogenous 5-HT-ergic tone and enhanced 5-HT release in response to amphetamine. Elevated 5-HT function and reduced activity of DAT are the probable reasons for the blunted effects of amphetamine in these mice. Lsamp(-/-) mice are a promising model to study the neurobiological mechanisms of deviant social behaviour and adaptation impairment observed in many psychiatric disorders.
authors.affiliation: Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. innos@ut.ee
authors.forename: Jürgen
authors.initials: J
authors.lastname: Innos
authors.forename: Este
authors.initials: E
authors.lastname: Leidmaa
authors.forename: Mari-Anne
authors.initials: MA
authors.lastname: Philips
authors.forename: Silva
authors.initials: S
authors.lastname: Sütt
authors.forename: Aet
authors.initials: A
authors.lastname: Alttoa
authors.forename: Jaanus
authors.initials: J
authors.lastname: Harro
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.forename: Eero
authors.initials: E
authors.lastname: Vasar
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003213:Conditioning, Psychological; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D015870:Gene Expression; D001523:Mental Disorders / Q000235:genetics* / Q000523:psychology; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D012201:Reward; D012701:Serotonin / Q000378:metabolism*; D012920:Social Behavior Disorders / Q000235:genetics* / Q000523:psychology; D013702:Temporal Lobe / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D050483:Dopamine Plasma Membrane Transport Proteins; D058851:GPI-Linked Proteins; C095362:limbic system-associated membrane protein; D012701:Serotonin; D000661:Amphetamine