{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:32:41Z","timestamp":1783441961771,"version":"3.54.6"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurosci"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Methamphetamine (MA) is a non-selective monoamine releaser and thus releases serotonin (5-HT), norepinephrine (NE) and dopamine (DA) from corresponding nerve terminals into synapses. DOI ((\u00b1)-2, 5-dimethoxy-4-iodoamphetamine) is a direct-acting serotonergic 5-HT<jats:sub>2A\/C<\/jats:sub> receptor agonist and induces the head-twitch response (HTR) via stimulation of 5-HT<jats:sub>2A<\/jats:sub> receptor in mice. While more selective serotonin releasers such as d-fenfluramine evoke the HTR, monoamine reuptake blockers (e.g., cocaine) suppress the DOI-evoked HTR via indirect stimulation of serotonergic 5-HT<jats:sub>1A<\/jats:sub>- and adrenergic \u0251<jats:sub>2<\/jats:sub>-receptors. Since the induction of HTR by DOI is age-dependent, we investigated whether: (1) during development MA can evoke the HTR by itself, and (2) acute pretreatment with either the selective 5-HT<jats:sub>2A<\/jats:sub> receptor antagonist EMD 281014 or low-doses of MA can: (i) modulate the DOI-induced HTR in mice across postnatal days 20, 30 and 60, and (ii) alter the DOI-induced c-<jats:italic>fos<\/jats:italic> expression in mice prefrontal cortex (PFC). To further explore the possible modulatory effect of MA on DOI-induced HTR, we investigated whether blockade of inhibitory serotonergic 5-HT<jats:sub>1A<\/jats:sub>- or adrenergic \u0251<jats:sub>2<\/jats:sub>-receptors by corresponding selective antagonists (WAY 100635 or RS 79948, respectively), can prevent the effect of MA on DOI-induced HTR during aging.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Although neither EMD 281014 nor MA by themselves could evoke the HTR, acute pretreatment with either EMD 281014 (0.01, 0.05 and 0.1\u00a0mg\/kg, i.p.) or MA (1, 2.5, 5\u00a0mg\/kg, i.p.), dose-dependently suppressed the DOI-induced HTR across ages. While WAY 100635 significantly reversed the inhibitory effect of MA in 20- and 30-day old mice, RS 79948 failed to significantly counter MA\u2019s inhibitory effect. Moreover, DOI significantly increased c-<jats:italic>fos<\/jats:italic> expressions in several PFC regions. EMD 281014 prevented the DOI-induced increases in c-<jats:italic>fos<\/jats:italic> expression. Despite the inhibitory effect of MA on DOI-induced HTR, MA alone or in combination with DOI, significantly increased c-<jats:italic>fos<\/jats:italic> expression in several regions of the PFC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The suppressive effect of MA on the DOI-evoked HTR appears to be mainly due to functional interactions between the HTR-inducing 5-HT<jats:sub>2A<\/jats:sub> receptor and the inhibitory 5-HT<jats:sub>1A<\/jats:sub> receptor. The MA-induced increase in c-<jats:italic>fos<\/jats:italic> expression in different PFC regions may be due to MA-evoked increases in synaptic concentrations of 5-HT, NE and\/or DA.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12868-021-00686-5","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T10:08:03Z","timestamp":1641290883000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["An ontogenic study of receptor mechanisms by which acute administration of low-doses of methamphetamine suppresses DOI-induced 5-HT2A-receptor mediated head-twitch response in mice"],"prefix":"10.1186","volume":"23","author":[{"given":"Yina","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seetha","family":"Chebolu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Lankireddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-099X","authenticated-orcid":false,"given":"Nissar A.","family":"Darmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"686_CR1","first-page":"802","volume":"155","author":"G Costa","year":"2020","unstructured":"Costa G, De Luca MA, Piras G, Marongiu J, Fattore L, Simola N. Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies. Neural Regen Res. 2020;155:802\u201316.","journal-title":"Neural Regen Res"},{"key":"686_CR2","unstructured":"World Drug Report. Stimulants. The United Nations Office on Drugs and Crime (UNODC). Sales No. E.19.XI.8. United Nations publication."},{"key":"686_CR3","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.tins.2012.05.006","volume":"359","author":"JF Marshall","year":"2012","unstructured":"Marshall JF, O\u2019Dell SJ. Methamphetamine influences on brain and behavior: unsafe at any speed? Trends Neurosci. 2012;359:536\u201345.","journal-title":"Trends Neurosci"},{"key":"686_CR4","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.eclinm.2019.09.014","volume":"16","author":"R McKetin","year":"2019","unstructured":"McKetin R, Leung J, Stockings E, Huo Y, Foulds J, Lappin JM, et al. Mental health outcomes associated with of the use of amphetamines: a systematic review and meta-analysis. EClinicalMedicine. 2019;16:81\u201397.","journal-title":"EClinicalMedicine"},{"key":"686_CR5","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1111\/j.1360-0443.2009.02564.x","volume":"1047","author":"CC Cruickshank","year":"2009","unstructured":"Cruickshank CC, Dyer KR. A review of the clinical pharmacology of methamphetamine. Addiction. 2009;1047:1085\u201399.","journal-title":"Addiction"},{"key":"686_CR6","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.pneurobio.2005.04.003","volume":"756","author":"D Sulzer","year":"2005","unstructured":"Sulzer D, Sonders MS, Poulsen NW, Galli A. Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005;756:406\u201333.","journal-title":"Prog Neurobiol"},{"key":"686_CR7","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1124\/jpet.106.115402","volume":"3211","author":"EA Reese","year":"2007","unstructured":"Reese EA, Bunzow JR, Arttamangkul S, Sonders MS, Grandy DK. Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine. J Pharmacol Exp Ther. 2007;3211:178\u201386.","journal-title":"J Pharmacol Exp Ther"},{"key":"686_CR8","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/j.1471-4159.2004.02501.x","volume":"902","author":"MD Berry","year":"2004","unstructured":"Berry MD. Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. J Neurochem. 2004;902:257\u201371.","journal-title":"J Neurochem."},{"key":"686_CR9","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/sj.npp.1300575","volume":"302","author":"LJ Madden","year":"2005","unstructured":"Madden LJ, Flynn CT, Zandonatti MA, May M, Parsons LH, Katner SN, et al. Modeling human methamphetamine exposure in nonhuman primates: chronic dosing in the rhesus macaque leads to behavioral and physiological abnormalities. Neuropsychopharmacology. 2005;302:350\u20139.","journal-title":"Neuropsychopharmacology"},{"key":"686_CR10","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.neuro.2019.12.006","volume":"77","author":"S Sabrini","year":"2020","unstructured":"Sabrini S, Russell B, Wang G, Lin J, Kirk I, Curley L. Methamphetamine induces neuronal death: evidence from rodent studies. Neurotoxicology. 2020;77:20\u20138.","journal-title":"Neurotoxicology"},{"key":"686_CR11","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.pbb.2014.09.012","volume":"126","author":"A Kim","year":"2014","unstructured":"Kim A, Mandyam CD. Methamphetamine affects cell proliferation in the medial prefrontal cortex: a new niche for toxicity. Pharmacol Biochem Behav. 2014;126:90\u20136.","journal-title":"Pharmacol Biochem Behav"},{"key":"686_CR12","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.pbb.2011.08.004","volume":"1001","author":"CJ Yuan","year":"2011","unstructured":"Yuan CJ, Quiocho JM, Kim A, Wee S, Mandyam CD. Extended access methamphetamine decreases immature neurons in the hippocampus which results from loss and altered development of neural progenitors without altered dynamics of the S-phase of the cell cycle. Pharmacol Biochem Behav. 2011;1001:98\u2013108.","journal-title":"Pharmacol Biochem Behav"},{"key":"686_CR13","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.drugalcdep.2012.11.016","volume":"1293","author":"WJ Panenka","year":"2013","unstructured":"Panenka WJ, Procyshyn RM, Lecomte T, MacEwan GW, Flynn SW, Honer WG, et al. Methamphetamine use: a comprehensive review of molecular, preclinical and clinical findings. Drug Alcohol Depend. 2013;1293:167\u201379.","journal-title":"Drug Alcohol Depend"},{"key":"686_CR14","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.neuropharm.2011.11.003","volume":"622","author":"CM Reichel","year":"2012","unstructured":"Reichel CM, Ramsey LA, Schwendt M, McGinty JF, See RE. Methamphetamine-induced changes in the object recognition memory circuit. Neuropharmacology. 2012;622:1119\u201326.","journal-title":"Neuropharmacology"},{"key":"686_CR15","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1002\/dta.1333","volume":"47\u20138","author":"CE Canal","year":"2012","unstructured":"Canal CE, Morgan D. Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model. Drug Test Anal. 2012;47\u20138:556\u201376.","journal-title":"Drug Test Anal"},{"key":"686_CR16","doi-asserted-by":"publisher","first-page":"107933","DOI":"10.1016\/j.neuropharm.2019.107933","volume":"167","author":"AL Halberstadt","year":"2020","unstructured":"Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD. Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology. 2020;167:107933.","journal-title":"Neuropharmacology."},{"key":"686_CR17","first-page":"115","volume":"1861","author":"NA Darmani","year":"1990","unstructured":"Darmani NA, Martin BR, Glennon RA. Withdrawal from chronic treatment with (+\/-)-DOI causes super-sensitivity to 5-HT2 receptor-induced head-twitch behaviour in mice. Eur J Pharmacol. 1990;1861:115\u20138.","journal-title":"Eur J Pharmacol."},{"key":"686_CR18","first-page":"101","volume":"2731","author":"R Schreiber","year":"1995","unstructured":"Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ. (1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A\/2C antagonists, D1 antagonists and 5-HT1A agonists. J Pharmacol Exp Ther. 1995;2731:101\u201312.","journal-title":"J Pharmacol Exp Ther"},{"key":"686_CR19","first-page":"699","volume":"2822","author":"DL Willins","year":"1997","unstructured":"Willins DL, Meltzer HY. Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats. J Pharmacol Exp Ther. 1997;2822:699\u2013706.","journal-title":"J Pharmacol Exp Ther"},{"key":"686_CR20","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.neuron.2007.01.008","volume":"533","author":"J Gonzalez-Maeso","year":"2007","unstructured":"Gonzalez-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, et al. Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron. 2007;533:439\u201352.","journal-title":"Neuron"},{"key":"686_CR21","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/S0031-9384(96)00323-X","volume":"606","author":"NA Darmani","year":"1996","unstructured":"Darmani NA, Shaddy J, Gerdes CF. Differential ontogenesis of three DOI-induced behaviors in mice. Physiol Behav. 1996;606:1495\u2013500.","journal-title":"Physiol Behav"},{"key":"686_CR22","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/S0091-3057(96)00108-6","volume":"553","author":"NA Darmani","year":"1996","unstructured":"Darmani NA, Reeves SL. The stimulatory and inhibitory components of cocaine\u2019s actions on the 5-HTP-induced 5-HT2A receptor response. Pharmacol Biochem Behav. 1996;553:387\u201396.","journal-title":"Pharmacol Biochem Behav"},{"key":"686_CR23","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/S0091-3057(97)00548-0","volume":"601","author":"NA Darmani","year":"1998","unstructured":"Darmani NA. Cocaine and selective monoamine uptake blockers (sertraline, nisoxetine, and GBR 12935) prevent the d-fenfluramine-induced head-twitch response in mice. Pharmacol Biochem Behav. 1998;601:83\u201390.","journal-title":"Pharmacol Biochem Behav"},{"key":"686_CR24","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1017\/S1461145714000455","volume":"1710","author":"HY Chiu","year":"2014","unstructured":"Chiu HY, Chan MH, Lee MY, Chen ST, Zhan ZY, Chen HH. Long-lasting alterations in 5-HT2A receptor after a binge regimen of methamphetamine in mice. Int J Neuropsychopharmacol. 2014;1710:1647\u201358.","journal-title":"Int J Neuropsychopharmacol"},{"key":"686_CR25","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1093\/ijnp\/pyy044","volume":"218","author":"LM McFadden","year":"2018","unstructured":"McFadden LM, Cordie R, Livermont T, Johansen A. Behavioral and serotonergic changes in the frontal cortex following methamphetamine self-administration. Int J Neuropsychopharmacol. 2018;218:758\u201363.","journal-title":"Int J Neuropsychopharmacol"},{"key":"686_CR26","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/0091-3057(90)90098-3","volume":"364","author":"NA Darmani","year":"1990","unstructured":"Darmani NA, Martin BR, Pandey U, Glennon RA. Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacol Biochem Behav. 1990;364:901\u20136.","journal-title":"Pharmacol Biochem Behav"},{"key":"686_CR27","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/0091-3057(91)90290-I","volume":"382","author":"NA Darmani","year":"1991","unstructured":"Darmani NA, Martin BR, Pandey U, Glennon RA. Inhibition of 5-HT2 receptor-mediated head-twitch response by cocaine via indirect stimulation of adrenergic alpha 2 and serotonergic 5-HT1A receptors. Pharmacol Biochem Behav. 1991;382:353\u20137.","journal-title":"Pharmacol Biochem Behav"},{"key":"686_CR28","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/0091-3057(93)90238-O","volume":"452","author":"NA Darmani","year":"1993","unstructured":"Darmani NA. Role of the inhibitory adrenergic alpha 2 and serotonergic 5-HT1A components of cocaine\u2019s actions on the DOI-induced head-twitch response in 5-HT2-receptor supersensitive mice. Pharmacol Biochem Behav. 1993;452:269\u201374.","journal-title":"Pharmacol Biochem Behav"},{"key":"686_CR29","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/S0014-2999(03)01992-7","volume":"4732\u20133","author":"GD Bartoszyk","year":"2003","unstructured":"Bartoszyk GD, van Amsterdam C, Bottcher H, Seyfried CA. EMD 281014, a new selective serotonin 5-HT2A receptor antagonist. Eur J Pharmacol. 2003;4732\u20133:229\u201330.","journal-title":"Eur J Pharmacol"},{"key":"686_CR30","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.ejphar.2004.06.065","volume":"4973","author":"V Fagerholm","year":"2004","unstructured":"Fagerholm V, Philipp M, Hein L, Scheinin M. [Ethyl-3H]RS-79948-197 alpha2-adrenoceptor autoradiography validation in alpha2-adrenoceptor knockout mice. Eur J Pharmacol. 2004;4973:301\u20139.","journal-title":"Eur J Pharmacol"},{"key":"686_CR31","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/0165-0270(89)90150-7","volume":"293","author":"M Dragunow","year":"1989","unstructured":"Dragunow M, Faull R. The use of c-fos as a metabolic marker in neuronal pathway tracing. J Neurosci Methods. 1989;293:261\u20135.","journal-title":"J Neurosci Methods"},{"key":"686_CR32","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/328632a0","volume":"3286131","author":"SP Hunt","year":"1987","unstructured":"Hunt SP, Pini A, Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature. 1987;3286131:632\u20134.","journal-title":"Nature"},{"key":"686_CR33","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s00213-011-2441-y","volume":"219","author":"L Wischhof","year":"2012","unstructured":"Wischhof L, Koch M. Pre-treatment with the mGlu2\/3 receptor agonist LY379268 attenuates DOI-induced impulsive responding and regional c-Fos protein expression. Psychopharmacology. 2012;219:387\u2013400.","journal-title":"Psychopharmacology"},{"key":"686_CR34","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/S0892-0362(99)00054-9","volume":"221","author":"NA Darmani","year":"2000","unstructured":"Darmani NA, Ahmad B. Early postnatal cocaine exposure causes sequential, dose-dependent, enduring but reversible supersensitivity in 5-HT2A receptor-mediated function during development in male mice. Neurotoxicol Teratol. 2000;221:61\u20139.","journal-title":"Neurotoxicol Teratol"},{"key":"686_CR35","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/0091-3057(94)00340-8","volume":"504","author":"NA Darmani","year":"1995","unstructured":"Darmani NA, Gerdes CF. Temporal differential adaptation of head-twitch and ear-scratch responses following administration of challenge doses of DOI. Pharmacol Biochem Behav. 1995;504:545\u201350.","journal-title":"Pharmacol Biochem Behav"},{"key":"686_CR36","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1016\/0024-3205(96)00428-6","volume":"5914","author":"NA Darmani","year":"1996","unstructured":"Darmani NA. Differential potentiation of L-tryptophan-induced head-twitch response in mice by cocaine and sertraline. Life Sci. 1996;5914:1109\u201319.","journal-title":"Life Sci"},{"key":"686_CR37","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1111\/j.1476-5381.2009.00578.x","volume":"1594","author":"MA Fox","year":"2010","unstructured":"Fox MA, Stein AR, French HT, Murphy DL. Functional interactions between 5-HT2A and presynaptic 5-HT1A receptor-based responses in mice genetically deficient in the serotonin 5-HT transporter (SERT). Br J Pharmacol. 2010;1594:879\u201387.","journal-title":"Br J Pharmacol"},{"key":"686_CR38","unstructured":"Paxinos G, Franklin KBJ. The mouse brain in stereotaxic coordinates, deluxe ed of the Atlas, 2nd ed. San Diego: Academic Press."},{"key":"686_CR39","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1111\/jnc.14959","volume":"1544","author":"G Kogias","year":"2020","unstructured":"Kogias G, Zheng F, Kalinichenko LS, Kornhuber J, Alzheimer C, Mielenz D, et al. Swiprosin1\/EFhd2 is involved in the monoaminergic and locomotor responses of psychostimulant drugs. J Neurochem. 2020;1544:424\u201340.","journal-title":"J Neurochem"},{"key":"686_CR40","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1016\/j.bcp.2013.04.004","volume":"8512","author":"AJ Eshleman","year":"2013","unstructured":"Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A. Substituted methcathinones differ in transporter and receptor interactions. Biochem Pharmacol. 2013;8512:1803\u201315.","journal-title":"Biochem Pharmacol"},{"key":"686_CR41","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/0304-3940(90)90520-J","volume":"1151","author":"MR Pranzatelli","year":"1990","unstructured":"Pranzatelli MR. Evidence for involvement of 5-HT2 and 5-HT1C receptors in the behavioral effects of the 5-HT agonist 1-(2,5-dimethoxy-4-iodophenyl aminopropane)-2 (DOI). Neurosci Lett. 1990;1151:74\u201380.","journal-title":"Neurosci Lett"},{"key":"686_CR42","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S1385-299X(98)00032-4","volume":"31","author":"G Sekerkova","year":"1998","unstructured":"Sekerkova G, Katarova Z, Szabo G. Using GADlacZ transgenic mice as a marker system for homotopic transplantation. Brain Res Brain Res Protoc. 1998;31:107\u201318.","journal-title":"Brain Res Brain Res Protoc"},{"key":"686_CR43","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0006-8993(84)91397-0","volume":"3111","author":"JO Marcusson","year":"1984","unstructured":"Marcusson JO, Morgan DG, Winblad B, Finch CE. Serotonin-2 binding sites in human frontal cortex and hippocampus. Selective loss of S-2A sites with age. Brain Res. 1984;3111:51\u20136.","journal-title":"Brain Res."},{"key":"686_CR44","first-page":"1051","volume":"2443","author":"Y Claustre","year":"1988","unstructured":"Claustre Y, Rouquier L, Scatton B. Pharmacological characterization of serotonin-stimulated phosphoinositide turnover in brain regions of the immature rat. J Pharmacol Exp Ther. 1988;2443:1051\u20136.","journal-title":"J Pharmacol Exp Ther"},{"key":"686_CR45","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/0006-8993(93)90286-V","volume":"6201","author":"B Arranz","year":"1993","unstructured":"Arranz B, Eriksson A, Mellerup E, Plenge P, Marcusson J. Effect of aging in human cortical pre- and postsynaptic serotonin binding sites. Brain Res. 1993;6201:163\u20136.","journal-title":"Brain Res"},{"key":"686_CR46","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1016\/0024-3205(94)00320-3","volume":"5520","author":"T Nabeshima","year":"1994","unstructured":"Nabeshima T, Yamada K, Hayashi T, Hasegawa T, Ishihara S, Kameyama T, et al. Changes in muscarinic cholinergic, PCP, GABAA, D1, and 5-HT2A receptor binding, but not in benzodiazepine receptor binding in the brains of aged rats. Life Sci. 1994;5520:1585\u201393.","journal-title":"Life Sci"},{"key":"686_CR47","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1002\/cne.902900205","volume":"2902","author":"SR Sesack","year":"1989","unstructured":"Sesack SR, Deutch AY, Roth RH, Bunney BS. Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin. J Comp Neurol. 1989;2902:213\u201342.","journal-title":"J Comp Neurol"},{"key":"686_CR48","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.neubiorev.2003.09.003","volume":"276","author":"CA Heidbreder","year":"2003","unstructured":"Heidbreder CA, Groenewegen HJ. The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics. Neurosci Biobehav Rev. 2003;276:555\u201379.","journal-title":"Neurosci Biobehav Rev"},{"key":"686_CR49","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1002\/(SICI)1098-2396(199709)27:1<79::AID-SYN8>3.0.CO;2-A","volume":"271","author":"DL Willins","year":"1997","unstructured":"Willins DL, Deutch AY, Roth BL. Serotonin 5-HT2A receptors are expressed on pyramidal cells and interneurons in the rat cortex. Synapse. 1997;271:79\u201382.","journal-title":"Synapse"},{"key":"686_CR50","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1093\/cercor\/bhh070","volume":"1410","author":"N Santana","year":"2004","unstructured":"Santana N, Bortolozzi A, Serrats J, Mengod G, Artigas F. Expression of serotonin1A and serotonin2A receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex. Cereb Cortex. 2004;1410:1100\u20139.","journal-title":"Cereb Cortex"},{"key":"686_CR51","doi-asserted-by":"publisher","first-page":"3864","DOI":"10.1523\/JNEUROSCI.20-10-03864.2000","volume":"2010","author":"DB Carr","year":"2000","unstructured":"Carr DB, Sesack SR. Projections from the rat prefrontal cortex to the ventral tegmental area: target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons. J Neurosci. 2000;2010:3864\u201373.","journal-title":"J Neurosci"},{"key":"686_CR52","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0306-4522(97)00372-2","volume":"831","author":"E Jodo","year":"1998","unstructured":"Jodo E, Chiang C, Aston-Jones G. Potent excitatory influence of prefrontal cortex activity on noradrenergic locus coeruleus neurons. Neuroscience. 1998;831:63\u201379.","journal-title":"Neuroscience"},{"key":"686_CR53","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.euroneuro.2013.07.005","volume":"242","author":"J Wallace","year":"2014","unstructured":"Wallace J, Jackson RK, Shotton TL, Munjal I, McQuade R, Gartside SE. Characterization of electrically evoked field potentials in the medial prefrontal cortex and orbitofrontal cortex of the rat: modulation by monoamines. Eur Neuropsychopharmacol. 2014;242:321\u201332.","journal-title":"Eur Neuropsychopharmacol"},{"key":"686_CR54","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1002\/cne.903130409","volume":"3134","author":"RP Vertes","year":"1991","unstructured":"Vertes RP. A PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat. J Comp Neurol. 1991;3134:643\u201368.","journal-title":"J Comp Neurol"},{"key":"686_CR55","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/0306-4522(91)90128-B","volume":"402","author":"R Araneda","year":"1991","unstructured":"Araneda R, Andrade R. 5-Hydroxytryptamine2 and 5-hydroxytryptamine 1A receptors mediate opposing responses on membrane excitability in rat association cortex. Neuroscience. 1991;402:399\u2013412.","journal-title":"Neuroscience"},{"key":"686_CR56","doi-asserted-by":"publisher","first-page":"4807","DOI":"10.1523\/JNEUROSCI.5113-03.2004","volume":"2420","author":"JC Beique","year":"2004","unstructured":"Beique JC, Campbell B, Perring P, Hamblin MW, Walker P, Mladenovic L, et al. Serotonergic regulation of membrane potential in developing rat prefrontal cortex: coordinated expression of 5-hydroxytryptamine (5-HT)1A, 5-HT2A, and 5-HT7 receptors. J Neurosci. 2004;2420:4807\u201317.","journal-title":"J Neurosci"},{"key":"686_CR57","doi-asserted-by":"publisher","first-page":"10094","DOI":"10.1523\/JNEUROSCI.1960-09.2009","volume":"2932","author":"NM Goodfellow","year":"2009","unstructured":"Goodfellow NM, Benekareddy M, Vaidya VA, Lambe EK. Layer II\/III of the prefrontal cortex: inhibition by the serotonin 5-HT1A receptor in development and stress. J Neurosci. 2009;2932:10094\u2013103.","journal-title":"J Neurosci"},{"key":"686_CR58","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.neuropharm.2011.01.015","volume":"613","author":"R Andrade","year":"2011","unstructured":"Andrade R. Serotonergic regulation of neuronal excitability in the prefrontal cortex. Neuropharmacology. 2011;613:382\u20136.","journal-title":"Neuropharmacology"},{"key":"686_CR59","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1113\/jphysiol.2005.086066","volume":"2","author":"ZW Zhang","year":"2005","unstructured":"Zhang ZW, Arsenault D. Gain modulation by serotonin in pyramidal neurones of the rat prefrontal cortex. J Physiol. 2005;2:379\u201394.","journal-title":"J Physiol"},{"key":"686_CR60","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1111\/j.1476-5381.1993.tb13727.x","volume":"1094","author":"SM Dursun","year":"1993","unstructured":"Dursun SM, Handley SL. The effects of alpha 2-adrenoceptor antagonists on the inhibition of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head shakes by 5-HT1A receptor agonists in the mouse. Br J Pharmacol. 1993;1094:1046\u201352.","journal-title":"Br J Pharmacol"},{"key":"686_CR61","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s007020050085","volume":"105","author":"NA Darmani","year":"1998","unstructured":"Darmani NA. The silent and selective 5-HT1A antagonist, WAY 100635, produces via an indirect mechanism, a 5-HT2A receptor-mediated behavior in mice during the day but not at night. J Neural Transm. 1998;105:635\u201343.","journal-title":"J Neural Transm"},{"key":"686_CR62","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.neuroscience.2010.04.046","volume":"1691","author":"A Marzo","year":"2010","unstructured":"Marzo A, Bai J, Caboche J, Vanhoutte P, Otani S. Cellular mechanisms of long-term depression induced by noradrenaline in rat prefrontal neurons. Neuroscience. 2010;1691:74\u201386.","journal-title":"Neuroscience"},{"key":"686_CR63","first-page":"36","volume":"4","author":"ET Weber","year":"2010","unstructured":"Weber ET, Andrade R. Htr2a gene and 5-HT(2A) receptor expression in the cerebral cortex studied using genetically modified mice. Front Neurosci. 2010;4:36.","journal-title":"Front Neurosci"},{"key":"686_CR64","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/0028-3908(82)90040-5","volume":"216","author":"SL Handley","year":"1982","unstructured":"Handley SL, Brown J. Effects on the 5-hydroxytryptamine-induced head-twitch of drugs with selective actions on alpha1 and alpha2-adrenoceptors. Neuropharmacology. 1982;216:507\u201310.","journal-title":"Neuropharmacology"}],"container-title":["BMC Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12868-021-00686-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12868-021-00686-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12868-021-00686-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T14:07:32Z","timestamp":1676124452000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurosci.biomedcentral.com\/articles\/10.1186\/s12868-021-00686-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["686"],"URL":"https:\/\/doi.org\/10.1186\/s12868-021-00686-5","relation":{},"ISSN":["1471-2202"],"issn-type":[{"value":"1471-2202","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,4]]},"assertion":[{"value":"19 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The article is based on previously published studies and is in line with the journal\u2019s ethical guidelines. The protocol was approved by the Western University of Health Sciences Institutional Animal Care and Use Committee (IACUC) and conducted with strict adherence to the recommendations in the guide for the Care and Use of Laboratory Animals of the National Institute of Health (Department of Health and Human Services Publication, revised, 2011).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The author(s) declare no potential conflicts of interest with respect to the research, authorship, and\/or publication of this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2"}}