Abstract
Dorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it is unknown if dorsal striatal dopamine hyperactivity is the cause or consequence of changes elsewhere in the CSTC circuit. Classical pharmacological and neurotoxic manipulations of the CSTC and other brain circuits suffer from various drawbacks related to off-target effects and adaptive changes. Chemogenetics, on the other hand, enables a highly selective targeting of specific neuronal populations within a given circuit. In this study, we developed a chemogenetic method for selective activation of dopamine neurons in the substantia nigra, which innervates the dorsal striatum in the rat. We used this model to investigate effects of targeted dopamine activation on CSTC circuit function, especially in fronto-cortical regions. We found that chemogenetic activation of these neurons increased movement (as expected with increased dopamine release), rearings and time spent in center, while also lower self-grooming. Furthermore, this activation increased prepulse inhibition of the startle response in females. Remarkably, we observed reduced [18F]FDG metabolism in the frontal cortex, following dopamine activation in the dorsal striatum, while total glutamate levels- in this region were increased. This result is in accord with clinical studies of increased [18F]FDG metabolism and lower glutamate levels in similar regions of the brain of people with OCD. Taken together, the present chemogenetic model adds a mechanistic basis with behavioral and translational relevance to prior clinical neuroimaging studies showing deficits in fronto-cortical glucose metabolism across a variety of clinical populations (e.g. addiction, risky decision-making, compulsivity or obesity).
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Graybiel AM. The basal ganglia. Curr Biol. 2000;10:R509–11. https://doi.org/10.1016/s0960-9822(00)00593-5.
Ahmari SE, Dougherty DD. Dissecting OCD circuits: from animal models to targeted treatments. Depress Anxiety. 2015;32:550–62.
Peters SK, Dunlop K, Downar J. Cortico-striatal-thalamic loop circuits of the salience network: a central pathway in psychiatric disease and treatment. Front Syst Neurosci. 2016;10:1–23.
Simpson EH, Kellendonk C. Insights About Striatal Circuit Function and Schizophrenia From a Mouse Model of Dopamine D2 Receptor Upregulation. Biol Psychiatry. 2017;81:21–30.
Howes OD, Kapur S. The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common Pathway. Schizophr Bull. 2009;35:549–62.
Denys D, de Vries F, Cath D, Figee M, Vulink N, Veltman DJ, et al. Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2013;23:1423–31.
Zuo C, Ma Y, Sun B, Peng S, Zhang H, Eidelberg D, et al. Metabolic Imaging of Bilateral Anterior Capsulotomy in Refractory Obsessive Compulsive Disorder: an FDG PET Study. J Cereb Blood Flow Metab. 2013;33:880–7.
Horwitz B, Swedo SE, Grady CL, Pietrini P, Schapiro MB, Rapoport JL, et al. Cerebral metabolic pattern in obsessive-compulsive disorder: Altered intercorrelations between regional rates of glucose utilization. Psychiatry Res Neuroimaging. 1991;40:221–37.
Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: The orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32:525–49.
Whiteside SP, Port JD, Abramowitz JS. A meta–analysis of functional neuroimaging in obsessive–compulsive disorder. Psychiatry Res Neuroimaging. 2004;132:69–79.
Haber SN. Corticostriatal circuitry. Dialogues Clin Neurosci. 2016;18:7–21.
Aoki Y, Aoki A, Suwa H. Reduction of N-acetylaspartate in the medial prefrontal cortex correlated with symptom severity in obsessive-compulsive disorder: Meta-analyses of 1 H-MRS studies. Transl Psychiatry. 2012;2:e153–10.
Rosenberg DR, Macmaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry. 2000;39:1096–103.
Rosenberg DR, Mirza Y, Russell A, Tang J, Smith JM, Banerjee SP, et al. Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry. 2004;43:1146–53.
Palner M, Kjaerby C, Knudsen GM, Cumming P. Effects of unilateral 6-OHDA lesions on [3H]-N- propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat. Neurochem Int. 2011;58:243–7.
Casteels C, Lauwers E, Bormans G, Baekelandt V, Van Laere K. Metabolic-dopaminergic mapping of the 6-hydroxydopamine rat model for Parkinson’s disease. Eur J Nucl Med Mol Imaging. 2008;35:124–34.
Sala-Bayo J, Fiddian L, Nilsson SRO, Hervig ME, McKenzie C, Mareschi A, et al. Dorsal and ventral striatal dopamine D1 and D2 receptors differentially modulate distinct phases of serial visual reversal learning. Neuropsychopharmacology. 2020;45:736–44.
Witten IB, Steinberg EE, Lee SY, Davidson TJ, Zalocusky KA, Brodsky M, et al. Recombinase-Driver Rat Lines: Tools, Techniques, and Optogenetic Application to Dopamine-Mediated Reinforcement. Neuron. 2011;72:721–33.
Roughan JV, Flecknell PA. Behavioural effects of laparotomy and analgesic effects of ketoprofen and carprofen in rats. Pain. 2001;90:65–74.
Keller SH, L’Estrade EN, Dall B, Palner M, Herth M. Quantification accuracy of a new HRRT high throughput rat hotel using transmission-based attenuation correction: A phantom study. 2016 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room-Temperature Semiconductor Detector Workshop (NSS/MIC/RTSD). 2016, pp. 1–3. https://doi.org/10.1109/NSSMIC.2016.8069467.
Baerentzen S, Casado-Sainz A, Lange D, Shalgunov V, Tejada IM, Xiong M, et al. The chemogenetic receptor ligand Clozapine N-oxide induces in vivo neuroreceptor occupancy and reduces striatal glutamate levels. Front Neurosci. 2019;13:187.
Hoenig K, Hochrein A, Quednow BB, Maier W, Wagner M. Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder. Biol Psychiatry. 2005;57:1153–8.
Ahmari SE, Risbrough VB, Geyer MA, Simpson HB. Impaired sensorimotor gating in unmedicated adults with obsessive-compulsive disorder. Neuropsychopharmacology. 2012;37:1216–23.
Manning EE, Wang AY, Saikali LM, Winner AS, Ahmari SE. Disruption of prepulse inhibition is associated with compulsive behavior severity and nucleus accumbens dopamine receptor changes in Sapap3 knockout mice. Sci Rep. 2021;11:9442.
Armbruster BN, Li X, Pausch MH, Herlitze S, Roth BL. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci USA. 2007;104:5163–8.
Salegio EA, Samaranch L, Kells AP, Mittermeyer G, San Sebastian W, Zhou S, et al. Axonal transport of adeno-associated viral vectors is serotype-dependent. Gene Ther. 2013;20:348–52.
Aschauer DF, Kreuz S, Rumpel S. Analysis of Transduction Efficiency, Tropism and Axonal Transport of AAV Serotypes 1, 2, 5, 6, 8 and 9 in the Mouse Brain. PLoS One. 2013;8:e76310.
San Sebastian W, Samaranch L, Heller G, Kells AP, Bringas J, Pivirotto P, et al. Adeno-associated virus type 6 is retrogradely transported in the non-human primate brain. Gene Ther. 2013;20:1178–83.
Szablowski JO, Lee-gosselin A, Lue B, Malounda D, Shapiro MG. Non-invasive control of neural circuits. Nat Biomed Eng. 2018;2:1–11.
Mahler SV, Brodnik ZD, Cox BM, Buchta WC, Bentzley BS, Cope ZA, et al. Chemogenetic manipulations of ventral tegmental area dopamine neurons reveal multifaceted roles in cocaine abuse. BioRxiv. 2018;39:503–18.
Cho J, Ryu S, Lee S, Kim J, Kim HI. Optimizing clozapine for chemogenetic neuromodulation of somatosensory cortex. Sci Rep. 2020;10:1–11.
Mimura K, Nagai Y, Inoue KI, Matsumoto J, Hori Y, Sato C, et al. Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets. iScience. 2021;24:103066. https://doi.org/10.1016/j.isci.2021.103066.
Sciolino NR, Plummer NW, Chen Y-W, Alexander GM, Robertson SD, Dudek SM, et al. Recombinase-Dependent Mouse Lines for Chemogenetic Activation of Genetically Defined Cell Types. Cell Rep. 2016;15:2563–73.
Dell’Anno MT, Caiazzo M, Leo D, Dvoretskova E, Medrihan L, Colasante G, et al. Remote control of induced dopaminergic neurons in parkinsonian rats. J Clin Investig. 2014;124:3215–29.
Bonaventura J, Eldridge MAG, Hu F, Gomez JL, Sanchez-Soto M, Abramyan AM, et al. High-potency ligands for DREADD imaging and activation in rodents and monkeys. Nat Commun. 2019;10:4627. https://doi.org/10.1038/s41467-019-12236-z.
Runegaard AH, Fitzpatrick CM, Woldbye DPD, Andreasen JT, Sørensen AT, Gether U. Modulating dopamine signaling and behavior with chemogenetics: concepts, progress, and challenges. Pharm Rev. 2019;71:123–56.
Jackson BP, Dietz SM, Wightman RM. Fast-scan cyclic voltammetry of 5-hydroxytryptamine. Anal Chem 1995;67:1115–20.
Wang S, Tan Y, Zhang JE, Luo M. Pharmacogenetic activation of midbrain dopaminergic neurons induces hyperactivity. Neurosci Bull. 2013;29:517–24.
Boender AJ, de Jong JW, Boekhoudt L, Luijendijk MCM, van der Plasse G, Adan RAH. Combined use of the canine adenovirus-2 and DREADD-technology to activate specific neural pathways in vivo. PLoS One. 2014;9:e95392.
Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463:3–33.
Carli M, Prontera C, Samanin R. Effect of 5-HT1A agonists on stress-induced deficit in open field locomotor activity of rats: Evidence that this model identifies anxiolytic-like activity. Neuropharmacology. 1989;28:471–6.
Sturman O, Germain PL, Bohacek J. Exploratory rearing: a context- and stress-sensitive behavior recorded in the open-field test. Stress. 2018;21:443–52.
Berridge KC, Aldridge JW. Super-stereotypy I: Enhancement of a complex movement sequence by systemic dopamine D1 agonists. Synapse. 2000;37:194–204.
Kalueff AV, Stewart AM, Song C, Berridge KC, Graybiel AM, Fentress JC. Neurobiology of rodent self-grooming and its value for translational neuroscience. Nat Rev Neurosci. 2016;17:45–59.
Ahmari SE, Spellman T, Douglass NL, Kheirbek MA, Simpson HB, Deisseroth K, et al. Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science. 2013;340:1234–9.
Ramírez-Armenta KI, Alatriste-León H, Verma-Rodríguez AK, Llanos-Moreno A, Ramírez-Jarquín JO, Tecuapetla F. Optogenetic inhibition of indirect pathway neurons in the dorsomedial striatum reduces excessive grooming in Sapap3-knockout mice. Neuropsychopharmacology. 2021. https://doi.org/10.1038/s41386-021-01161-9.
Lu J, Cheng Y, Xie X, Woodson K, Bonifacio J, Disney E, et al. Whole-Brain Mapping of Direct Inputs to Dopamine D1 and D2 Receptor-Expressing Medium Spiny Neurons in the Posterior Dorsomedial Striatum. Eneuro. 2020. https://doi.org/10.1523/ENEURO.0348-20.2020.
Bubser M, Koch M. Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions of the medial prefrontal cortex. Psychopharmacology. 1994;113:487–92.
Zavitsanou K. Dopamine antagonists in the orbital prefrontal cortex reduce prepulse inhibition of the acoustic startle reflex in the rat. Pharm Biochem Behav. 1999;63:55–61.
Bikovsky L, Hadar R, Soto-Montenegro ML, Klein J, Weiner I, Desco M, et al. Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia. Exp Neurol. 2016;283:142–50.
Rohleder C, Wiedermann D, Neumaier B, Drzezga A, Timmermann L, Graf R, et al. The Functional Networks of Prepulse Inhibition: Neuronal Connectivity Analysis Based on FDG-PET in Awake and Unrestrained Rats. Front Behav Neurosci. 2016;10:148.
Swerdlow NR, Geyer MA, Braff DL. Neural circuit regulation of prepulse inhibition of startle in the rat: Current knowledge and future challenges. Psychopharmacology. 2001;156:194–215.
Koch M, Fendt M, Kretschmer BD. Role of the substantia nigra pars reticulata in sensorimotor gating, measured by prepulse inhibition of startle in rats. Behav Brain Res. 2000;117:153–62.
Ahmari SE, Risbrough VB, Geyer MA, Simpson HB. Prepulse inhibition deficits in obsessive-compulsive disorder are more pronounced in females. Neuropsychopharmacology. 2016;41:2963–4.
Rodrigues S, Salum C, Ferreira TL. Dorsal striatum D1-expressing neurons are involved with sensorimotor gating on prepulse inhibition test. J Psychopharmacol. 2017. https://doi.org/10.1177/0269881116686879.
Bortolato M, Aru GN, Fà M, Frau R, Orrù M, Salis P, et al. Activation of D1, but not D2 receptors potentiates dizocilpine-mediated disruption of prepulse inhibition of the startle. Neuropsychopharmacology. 2005;30:561–74.
Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl). 2001;156:117–54. https://doi.org/10.1007/s002130100811.
Weber M, Chang W-L, Breier MR, Yang A, Millan MJ, Swerdlow NR. The effects of the dopamine D2 agonist sumanirole on prepulse inhibition in rats. Eur Neuropsychopharmacol. 2010;20:421–5.
Plappert CF, Pilz PKD, Schnitzler H-U. Factors governing prepulse inhibition and prepulse facilitation of the acoustic startle response in mice. Behav Brain Res. 2004;152:403–12.
Swerdlow N. Discrepant findings of clozapine effects on prepulse inhibition of startle: is it the route or the rat? Neuropsychopharmacology. 1998;18:50–56.
Faraday MM. Rat sex and strain differences in responses to stress. Physiol Behav. 2002;75:507–22.
Lehmann J, Pryce CR, Feldon J. Sex differences in the acoustic startle response and prepulse inhibition in Wistar rats. Behav Brain Res. 1999;104:113–7.
Tylš F, Páleníček T, Kadeřábek L, Lipski M, Kubešová A, Horáček J. Sex differences and serotonergic mechanisms in the behavioural effects of psilocin. Behav Pharmacol. 2016;27:309–20.
Baldan Ramsey LC, Xu M, Wood N, Pittenger C. Lesions of the dorsomedial striatum disrupt prepulse inhibition. Neuroscience. 2011;180:222–8.
Ilg AK, Enkel T, Bartsch D, Bähner F. Behavioral Effects of Acute Systemic Low-Dose Clozapine in Wild-Type Rats: Implications for the Use of DREADDs in Behavioral Neuroscience. Front Behav Neurosci. 2018;12:173. https://doi.org/10.3389/fnbeh.2018.00173.
MacLaren DAA, Browne RW, Shaw JK, Krishnan Radhakrishnan S, Khare P, Espana RA, et al. Clozapine N-Oxide Administration Produces Behavioral Effects in Long-Evans Rats: Implications for Designing DREADD Experiments. ENeuro. 2016;3:219–16.
Gomez JL, Bonaventura J, Lesniak W, Mathews WB, Sysa-shah P, Rodriguez LA, et al. Chemogenetics revealed: dreadd occupancy and activation via converted clozapine. Science. 2017;357:503–7.
De Carolis L, Stasi MA, Serlupi-Crescenzi O, Borsini F, Nencini P. The effects of clozapine on quinpirole-induced non-regulatory drinking and prepulse inhibition disruption in rats. Psychopharmacology. 2010;212:105–15.
Apetz N, Kordys E, Simon M, Mang B, Aswendt M, Wiedermann D, et al. Effects of subthalamic deep brain stimulation on striatal metabolic connectivity in a rat hemiparkinsonian model. Dis Model Mech. 2019;12:dmm039065. https://doi.org/10.1242/dmm.039065.
Urban DJ, Zhu H, Marcinkiewcz CA, Michaelides M, Oshibuchi H, Rhea D, et al. Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons. Neuropsychopharmacology. 2016;41:1404–15. https://doi.org/10.1038/npp.2015.293. Epub 2015 Sep 18.
Michaelides M, Anderson SAR, Ananth M, Smirnov D, Thanos PK, Neumaier JF, et al. Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks. J Clin Investig. 2013;123:5342–50.
Servaes S, Glorie D, Verhaeghe J, Wyffels L, Stroobants S, Staelens S. [18F]-FDG PET neuroimaging in rats with quinpirole-induced checking behavior as a model for obsessive compulsive disorder. Psychiatry Res Neuroimaging. 2016;257:31–38.
Borghammer P, Cumming P, Aanerud J, Gjedde A. Artefactual subcortical hyperperfusion in PET studies normalized to global mean: Lessons from Parkinson’s disease. Neuroimage. 2009;45:249–57.
Moffett JR, Namboodiri MAA, Neale JH. Enhanced carbodiimide fixation for immunohistochemistry: Application to the comparative distributions of N-acetylaspartylglutamate and N- acetylaspartate immunoreactivities in rat brain. J Histochem Cytochem. 1993;41:559–70.
Bak LK, Schousboe A, Waagepetersen HS. The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem. 2006;98:641–53.
Agarwal N, Renshaw PF. Proton MR spectroscopy - Detectable major neurotransmitters of the brain: Biology and possible clinical applications. Am J Neuroradiol. 2012;33:595–602.
Zhao J, Ramadan E, Cappiello M, Wroblewska B, Bzdega T, Neale JH. NAAG inhibits KCl-induced [3H]-GABA release via mGluR3, cAMP, PKA and L-type calcium conductance. Eur J Neurosci. 2001;13:340–6.
Sulzer D, Joyce MP, Lin L, Geldwert D, Haber SN, Hattori T, et al. Dopamine neurons make glutamatergic synapses in vitro. J Neurosci. 1998;18:4588–602.
Trudeau LÉ. Glutamate co-transmission as an emerging concept in monoamine neuron function. J Psychiatry Neurosci. 2004;29:296–310.
Joo YH, Kim YK, Choi IG, Kim HJ, Son YD, Kim HK, et al. In vivo glucose metabolism and glutamate levels in mGluR5 knockout mice: a multimodal neuroimaging study using [18F]FDG microPET and MRS. EJNMMI Res. 2020;10:116. https://doi.org/10.1186/s13550-020-00716-z.
Wang Z, Maia TV, Marsh R, Colibazzi T, Gerber A, Peterson BS. The neural circuits that generate tics in Tourette’s syndrome. Am J Psychiatry. 2011;168:1326–37.
Figee M, Luigjes J, Smolders R, Valencia-Alfonso CE, Van Wingen G, De, et al. Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder. Nat Neurosci. 2013;16:386–7.
Nordstrom EJ, Bittner KC, McGrath MJ, Parks CR, Burton FH. Hyperglutamatergic cortico-striato-thalamo-cortical circuit breaker drugs alleviate tics in a transgenic circuit model of Tourette’s syndrome. Brain Res. 2015;1629:38–53.
Ceccherini-Nelli A, Guazzelli M. Treatment of refractory OCD with the dopamine agonist bromocriptine. J Clin Psychiatry. 1994;55:415–6.
Acknowledgements
Structural reference MR image is generously provided by Kristian Nygaard Mortensen, Center for Translational Neuromedicine, University of Copenhagen. Technical expertise regarding acoustic startle response and prepulse inhibition was generously provided by Kim Fejgin at H. Lundbeck. Radiochemical support was generously provided by Matthias M. Herth and Vladimir Shalgunov, Department of Drug Design and Pharmacology, University of Copenhagen. Statistical discussions with Professor Todd Ogden, Department of Biostatistics, Columbia University, NY. Professor, DM Gitte M. Knudsen, head of the Neurobiology Research Unit, Copenhagen University Hospital, offered her support and guidance for students and researchers throughout the project.
Funding
Funding for this project was provided to MP by the Lundbeck Foundation (R192-2015-1591 and R194-2015-1589), Augustinus Foundation (18-3746 and 17-1982, Independent Research Fund Denmark (5053-00036B), Savværksejer Jeppe Juhls og Hustrus Ovita Juhls Mindelegat and Købmand i Odense Johann og Hanne Weimann født Seedorffs Legat. MS was supported by a Marie Curie Sklodowska Fellowship. CK was supported by grants from the Augustinus Fonden (16-3735) and the Independent Research Fond Denmark (100948). MP is collaborating with the company Compass Pathways Plc (London, UK). MS is a member of the scientific advisory board of Roche Pharmaceuticals. The remaining authors have nothing to disclose. Parts of this manuscript have been presented as posters and preprints Casado et al. Eur. Neuropsych. 27, S689, Baerentzen et al JCBFM 37, 221 and bioRxiv 2021.02.11.430770.
Author information
Authors and Affiliations
Contributions
Conceptualization, CK, MP; methodology, ACS, FG, SLB, DL, SHK, AR, SM, IM, HL, CS, CK, MP; validation, ACS, SLB, MS, SHK, SM, PMF, CK, CS, PC, MP; formal analysis, ACS, SLB, FG, SM, DL, SHK, AR, CS, MP; investigation, PC, MP; resources, AC, MP; data curation, ACS, FG, SLB, DL, AR, IM, MS, CS, PMF, MP; writing—original draft preparation, MP; writing—review and editing, MS, PMF, PC, MP; visualization, MP; supervision, CS, CK, MP; funding acquisition, ACS, MP. All authors have read and agreed to the published version of the manuscript.
Corresponding author
Ethics declarations
Competing interests
MP is collaborating with the company Compass Pathways Plc (London, UK). MS is a member of the scientific advisory board of Roche Pharmaceuticals. The remaining authors have nothing to disclose.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Casado-Sainz, A., Gudmundsen, F., Baerentzen, S.L. et al. Dorsal striatal dopamine induces fronto-cortical hypoactivity and attenuates anxiety and compulsive behaviors in rats. Neuropsychopharmacol. 47, 454–464 (2022). https://doi.org/10.1038/s41386-021-01207-y
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41386-021-01207-y
This article is cited by
-
The effect of selective nigrostriatal dopamine excess on behaviors linked to the cognitive and negative symptoms of schizophrenia
Neuropsychopharmacology (2023)
-
Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats
Molecular Psychiatry (2023)
-
Chemogenetics for cell-type-specific modulation of signalling and neuronal activity
Nature Reviews Methods Primers (2023)
-
Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior
Psychopharmacology (2022)
