CHL1 Depletion Affects Dopamine Receptor D2-dependent Modulation of Mouse Behavior

Overview

Journal Front Behav Neurosci

Specialty Psychology

Date 2023 Nov 29

PMID 38025382

Authors

Luciana Fernandes

Ralf Kleene

Ludovica Congiu

Sandra Freitag

Matthias Kneussel

Gabriele Loers

Melitta Schachner

Affiliations

Soon will be listed here.

Abstract

Introduction: The dopaminergic system plays a key role in the appropriate functioning of the central nervous system, where it is essential for emotional balance, arousal, reward, and motor control. The cell adhesion molecule close homolog of L1 (CHL1) contributes to dopaminergic system development, and CHL1 and the dopamine receptor D2 (D2R) are associated with mental disorders like schizophrenia, addiction, autism spectrum disorder and depression.

Methods: Here, we investigated how the interplay between CHL1 and D2R affects the behavior of young adult male and female wild-type (CHL+/+) and CHL1-deficient (CHL1-/-) mice, when D2R agonist quinpirole and antagonist sulpiride are applied.

Results: Low doses of quinpirole (0.02 mg/kg body weight) induced hypolocomotion of CHL1+/+ and CHL1-/- males and females, but led to a delayed response in CHL1-/- mice. Sulpiride (1 mg/kg body weight) affected locomotion of CHL1-/- females and social interaction of CHL1+/+ females as well as social interactions of CHL1-/- and CHL1+/+ males. Quinpirole increased novelty-seeking behavior of CHL1-/- males compared to CHL1+/+ males. Vehicle-treated CHL1-/- males and females showed enhanced working memory and reduced stress-related behavior.

Discussion: We propose that CHL1 regulates D2R-dependent functions . Deficiency of CHL1 leads to abnormal locomotor activity and emotionality, and to sex-dependent behavioral differences.

References

Kebabian J, Calne D . Multiple receptors for dopamine. Nature. 1979; 277(5692):93-6. DOI: 10.1038/277093a0. View

Pinoli M, Marino F, Cosentino M . Dopaminergic Regulation of Innate Immunity: a Review. J Neuroimmune Pharmacol. 2017; 12(4):602-623. DOI: 10.1007/s11481-017-9749-2. View

van den Buuse M . Central effects of quinpirole on blood pressure of spontaneously hypertensive rats. J Pharmacol Exp Ther. 1992; 262(1):303-11. View

Chen S, Lu K, Ko H, Huang T, Hao J, Yan Y . Parcellation of the striatal complex into dorsal and ventral districts. Proc Natl Acad Sci U S A. 2020; 117(13):7418-7429. PMC: 7132256. DOI: 10.1073/pnas.1921007117. View

Anzalone A, Lizardi-Ortiz J, Ramos M, De Mei C, Hopf F, Iaccarino C . Dual control of dopamine synthesis and release by presynaptic and postsynaptic dopamine D2 receptors. J Neurosci. 2012; 32(26):9023-34. PMC: 3752062. DOI: 10.1523/JNEUROSCI.0918-12.2012. View

Ponnusamy R, Nissim H, Barad M . Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice. Learn Mem. 2005; 12(4):399-406. PMC: 1183258. DOI: 10.1101/lm.96605. View

Usiello A, Baik J, Rouge-Pont F, Picetti R, Dierich A, Lemeur M . Distinct functions of the two isoforms of dopamine D2 receptors. Nature. 2000; 408(6809):199-203. DOI: 10.1038/35041572. View

Ramos A . Animal models of anxiety: do I need multiple tests?. Trends Pharmacol Sci. 2008; 29(10):493-8. DOI: 10.1016/j.tips.2008.07.005. View

Arias-Carrion O, Poppel E . Dopamine, learning, and reward-seeking behavior. Acta Neurobiol Exp (Wars). 2008; 67(4):481-8. DOI: 10.55782/ane-2007-1664. View

10.

Sakurai K, Migita O, Toru M, Arinami T . An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol Psychiatry. 2002; 7(4):412-5. DOI: 10.1038/sj.mp.4000973. View

11.

Lewis C, Levinson D, Wise L, DeLisi L, Straub R, Hovatta I . Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet. 2003; 73(1):34-48. PMC: 1180588. DOI: 10.1086/376549. View

12.

Montag-Sallaz M, Baarke A, Montag D . Aberrant neuronal connectivity in CHL1-deficient mice is associated with altered information processing-related immediate early gene expression. J Neurobiol. 2003; 57(1):67-80. DOI: 10.1002/neu.10254. View

13.

Fu J, Wang T, Fu Z, Li T, Zhang X, Zhao J . Case Report: A Case Report and Literature Review of 3p Deletion Syndrome. Front Pediatr. 2021; 9:618059. PMC: 7902511. DOI: 10.3389/fped.2021.618059. View

14.

Dal Toso R, Sommer B, Ewert M, Herb A, Pritchett D, Bach A . The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J. 1989; 8(13):4025-34. PMC: 401577. DOI: 10.1002/j.1460-2075.1989.tb08585.x. View

15.

Mandic-Maravic V, Grujicic R, Milutinovic L, Munjiza-Jovanovic A, Pejovic-Milovancevic M . Dopamine in Autism Spectrum Disorders-Focus on D2/D3 Partial Agonists and Their Possible Use in Treatment. Front Psychiatry. 2022; 12:787097. PMC: 8850940. DOI: 10.3389/fpsyt.2021.787097. View

16.

Sams-Dodd F . Effects of dopamine agonists and antagonists on PCP-induced stereotyped behaviour and social isolation in the rat social interaction test. Psychopharmacology (Berl). 1998; 135(2):182-93. DOI: 10.1007/s002130050500. View

17.

Jakovcevski I, Siering J, Hargus G, Karl N, Hoelters L, Djogo N . Close homologue of adhesion molecule L1 promotes survival of Purkinje and granule cells and granule cell migration during murine cerebellar development. J Comp Neurol. 2009; 513(5):496-510. DOI: 10.1002/cne.21981. View

18.

Tam G, van de Lagemaat L, Redon R, Strathdee K, Croning M, Malloy M . Confirmed rare copy number variants implicate novel genes in schizophrenia. Biochem Soc Trans. 2010; 38(2):445-51. DOI: 10.1042/BST0380445. View

19.

Lalonde R . The neurobiological basis of spontaneous alternation. Neurosci Biobehav Rev. 2002; 26(1):91-104. DOI: 10.1016/s0149-7634(01)00041-0. View

20.

Leshchynska I, Sytnyk V, Richter M, Andreyeva A, Puchkov D, Schachner M . The adhesion molecule CHL1 regulates uncoating of clathrin-coated synaptic vesicles. Neuron. 2006; 52(6):1011-25. DOI: 10.1016/j.neuron.2006.10.020. View