Abstract
Rationale
MK801, like other NMDA receptor open-channel blockers (e.g., ketamine and phencyclidine), increases the locomotor activity of rats and mice. Whether this behavioral effect ultimately relies on monoamine neurotransmission is of dispute.
Objective
The purpose of this study was to determine whether these psychopharmacological effects and underlying neural mechanisms vary according to sex and age.
Methods
Across four experiments, male and female preweanling and adolescent rats were pretreated with vehicle, the monoamine-depleting agent reserpine (1 or 5 mg/kg), the dopamine (DA) synthesis inhibitor ∝-methyl-DL-p-tyrosine (AMPT), the serotonin (5-HT) synthesis inhibitor 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), or both AMPT and PCPA. The locomotor activity of preweanling and adolescent rats was then measured after saline or MK801 (0.3 mg/kg) treatment.
Results
As expected, MK801 increased the locomotor activity of all age groups and both sexes, but the stimulatory effects were significantly less pronounced in male adolescent rats. Preweanling rats and adolescent female rats were more sensitive to the effects of DA and 5-HT synthesis inhibitors, as AMPT and PCPA caused only small reductions in the MK801-induced locomotor activity of male adolescent rats. Co-administration of AMPT+PCPA or high-dose reserpine (5 mg/kg) treatment substantially reduced MK801-induced locomotor activity in both age groups and across both sexes.
Conclusions
These results, when combined with other recent studies, show that NMDA receptor open-channel blockers cause pronounced age-dependent behavioral effects that can vary according to sex. The neural changes underlying these sex and age differences appear to involve monoamine neurotransmission.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adams B, Moghaddam B (1998) Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine. J Neurosci 18:5545–5554. https://doi.org/10.1523/JNEUROSCI.18-14-05545.1998
Andersen SL, Teicher MH (2000) Sex differences in dopamine receptors and their relevance to ADHD. Neurosci Biobehav Rev 24:137–141. https://doi.org/10.1016/s0149-7634(99)00044-5
Andersen SL, Rutstein M, Benzo JM, Hostetter JC, Teicher MH (1997) Sex differences in dopamine receptor overproduction and elimination. Neuroreport 8:1495–1498. https://doi.org/10.1097/00001756-199704140-00034
Andiné P, Widermark N, Axelsson R, Nyberg G, Olofsson U, Mårtensson E, Sandberg M (1999) Characterization of MK-801-induced behavior as a putative rat model of psychosis. J Pharmacol Exp Ther 290:1393–1408
Blanchard DC, Blanchard RJ, De Padua Carobrez A, Veniegas R, Rodgers RJ, Shepherd JK (1992) MK-801 produces a reduction in anxiety-related antipredator defensiveness in male and female rats and a gender-dependent increase in locomotor behavior. Psychopharmacology 108:352–362. https://doi.org/10.1007/bf02245123
Bolshakov KV, Gmiro VE, Tikhonov DB, Magazanik LG (2003) Determinants of trapping block of N-methyl-D-aspartate receptor channels. J Neurochem 87:56–65. https://doi.org/10.1046/j.1471-4159.2003.01956.x
Callaway CW, Kuczenski R, Segal DS (1989) Reserpine enhances amphetamine stereotypies without increasing amphetamine-induced changes in striatal dialysate dopamine. Brain Res 505:83–90. https://doi.org/10.1016/0006-8993(89)90118-2
Campbell BA, Lytle LD, Fibiger HC (1969) Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science 166:635–637. https://doi.org/10.1126/science.166.3905.635
Can A, Zanos P, Moaddel R, Kang HJ, Dossou KS, Wainer IW, Cheer JF, Frost DO, Huang XP, Gould TD (2016) Effects of ketamine and ketamine metabolites on evoked striatal dopamine release, dopamine receptors, and monoamine transporters. J Pharmacol Exp Ther 359:159–170. https://doi.org/10.1124/jpet.116.235838
Carlsson M, Carlsson A (1988) A regional study of sex differences in rat brain serotonin. Prog Neuro-Psychopharmacol Biol Psychiatry 12:53–61. https://doi.org/10.1016/0278-5846(88)90061-9
Carlsson M, Svensson K, Eriksson E, Carlsson A (1985) Rat brain serotonin: biochemical and functional evidence for a sex difference. J Neural Transm 63:297–313. https://doi.org/10.1007/bf01252033
Castellani S, Adams PM (1981) Acute and chronic phencyclidine effects on locomotor activity, stereotypy and ataxia in rats. Eur J Pharmacol 73:143–154. https://doi.org/10.1016/0014-2999(81)90086-8
Crawford CA, Moran AE, Baum TA, Apodaca MG, Montejano NR, Park GI, Gomez V, McDougall SA (2020) Effects of monoamine depletion on the ketamine-induced locomotor activity of preweanling, adolescent, and adult rats: sex and age differences. Behav Brain Res 379:112267. https://doi.org/10.1016/j.bbr.2019.112267
Criswell HE, Johnson KB, Mueller RA, Breese GR (1993) Evidence for involvement of brain dopamine and other mechanisms in the behavioral action of the N-methyl-D-aspartic acid antagonist MK-801 in control and 6-hydroxydopamine-lesioned rats. J Pharmacol Exp Ther 265:1001–1010
Cummings TJ, Walker PD (1996) Serotonin depletion exacerbates changes in striatal gene expression following quinolinic acid injection. Brain Res 743:240–248. https://doi.org/10.1016/s0006-8993(96)01053-0
Cyr M, Ghribi O, Thibault C, Morissette M, Landry M, Di Paolo T (2001) Ovarian steroids and selective estrogen receptor modulators activity on rat brain NMDA and AMPA receptors. Brain Res Rev 37:153–161. https://doi.org/10.1016/s0165-0173(01)00115-1
Duke MA, O'Neal J, McDougall SA (1997) Ontogeny of dopamine agonist-induced sensitization: role of NMDA receptors. Psychopharmacology 129:153–160. https://doi.org/10.1007/s002130050175
Feinstein I, Kritzer MF (2013) Acute N-methyl-D-aspartate receptor hypofunction induced by MK801 evokes sex-specific changes in behaviors observed in open-field testing in adult male and proestrus female rats. Neuroscience 228:200–214. https://doi.org/10.1016/j.neuroscience.2012.10.026
Fernandes A, Wojcik T, Baireddy P, Pieschl R, Newton A, Tian Y, Hong Y, Bristow L, Li YW (2015) Inhibition of in vivo [3H]MK-801 binding by NMDA receptor open channel blockers and GluN2B antagonists in rats and mice. Eur J Pharmacol 766:1–8. https://doi.org/10.1016/j.ejphar.2015.08.044
Finn IB, Iuvone PM, Holtzman SG (1990) Depletion of catecholamines in the brain of rats differentially affects stimulation of locomotor activity by caffeine, d-amphetamine, and methylphenidate. Neuropharmacology 29:625–631. https://doi.org/10.1016/0028-3908(90)90023-k
Ford LM, Norman AB, Sanberg PR (1989) The topography of MK-801-induced locomotor patterns in rats. Physiol Behav 46:755–758. https://doi.org/10.1016/0031-9384(89)90363-6
Frantz K, Van Hartesveldt C (1999a) The locomotor effects of MK801 in the nucleus accumbens of developing and adult rats. Eur J Pharmacol 368:125–135. https://doi.org/10.1016/s0014-2999(99)00009-6
Frantz K, Van Hartesveldt C (1999b) Locomotion elicited by MK801 in developing and adult rats: temporal, environmental, and gender effects. Eur J Pharmacol 369:145–157. https://doi.org/10.1016/s0091-3057(99)00162-8
French ED, Ceci A (1990) Non-competitive N-methyl-D-aspartate antagonists are potent activators of ventral tegmental A10 dopamine neurons. Neurosci Lett 119:159–162. https://doi.org/10.1016/0304-3940(90)90823-r
Gartside SE, Cole AJ, Williams AP, McQuade R, Judge SJ (2007) AMPA and NMDA receptor regulation of firing activity in 5-HT neurons of the dorsal and median raphe nuclei. Eur J Neurosci 25:3001–3008. https://doi.org/10.1111/j.1460-9568.2007.05577.x
Giordano M, Mejía-Viggiano MC (2001) Gender differences in spontaneous and MK-801-induced activity after striatal lesions. Brain Res Bull 56:553–561. https://doi.org/10.1016/s0361-9230(01)00627-x
Glasgow NG, Wilcox MR, Johnson JW (2018) Effects of Mg2+ on recovery of NMDA receptors from inhibition by memantine and ketamine reveal properties of a second site. Neuropharmacology 137:344–358. https://doi.org/10.1016/j.neuropharm.2018.05.017
Hancock PJ, Stamford JA (1999) Stereospecific effects of ketamine on dopamine efflux and uptake in the rat nucleus accumbens. Br J Anaesth 82:603–608. https://doi.org/10.1093/bja/82.4.603
Hiramatsu M, Cho AK, Nabeshima T (1989) Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine. Eur J Pharmacol 166:359–366. https://doi.org/10.1016/0014-2999(89)90346-4
Hoffman DC (1992) Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats. J Neural Transm 89:1–10. https://doi.org/10.1007/bf01245347
Holson RR, Pearce B (1992) Principles and pitfalls in the analysis of prenatal treatment effects in multiparous species. Neurotoxicol Teratol 14:221–228. https://doi.org/10.1016/0892-0362(92)90020-B
Hönack D, Löscher W (1993) Sex differences in NMDA receptor mediated responses in rats. Brain Res 620:167–170. https://doi.org/10.1016/0006-8993(93)90287-w
Huettner JE, Bean BP (1988) Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci U S A 85:1307–1311. https://doi.org/10.1073/pnas.85.4.1307
Huynh H, Feldt LS (1976) Estimation of the Box correction for degrees of freedom from sample data in randomized block and split-plot designs. J Educ Stat 1:69–82. https://doi.org/10.2307/1164736
Insel TR, Miller LP, Gelhard RE (1990) The ontogeny of excitatory amino acid receptors in rat forebrain—I. N-methyl-D-aspartate and quisqualate receptors. Neuroscience 35:31–43. https://doi.org/10.1016/0306-4522(90)90117-m
Jackisch R, Link T, Neufang B, Koch R (1992) Studies on the mechanism of action of the antiparkinsonian drugs memantine and amantadine: no evidence for direct dopaminomimetic or antimuscarinic properties. Arch Int Pharmacodyn Ther 320:21–42
Jacobs PS, Taylor BM, Bardgett ME (2000) Maturation of locomotor and Fos responses to the NMDA antagonists, PCP and MK-801. Dev Brain Res 122:91–95. https://doi.org/10.1016/s0165-3806(00)00059-6
Kiss JP, Tóth E, Lajtha A, Vizi ES (1994) NMDA receptors are not involved in the MK-801-induced increase of striatal dopamine release in rat: a microdialysis study. Brain Res 641:145–148. https://doi.org/10.1016/0006-8993(94)91828-7
Kuczenski R (1983) Biochemical actions of amphetamine and other stimulants. In: Creese I (ed) Stimulants: Neurochemical, behavioral and clinical perspectives. Raven Press, New York, pp 31–61
Kuribara H, Uchihashi Y (1993) SCH 23390 equivalently, but YM-09151-2 differentially reduces the stimulant effects of methamphetamine, MK-801 and ketamine: assessment by discrete shuttle avoidance in mice. Jpn J Pharmacol 62:111–114. https://doi.org/10.1254/jjp.62.111
Kuribara H, Asami T, Ida I, Tadokoro S (1992) Characteristics of the ambulation-increasing effect of the noncompetitive NMDA antagonist MK-801 in mice: assessment by the coadministration with central-acting drugs. Jpn J Pharmacol 58:11–18. https://doi.org/10.1254/jjp.58.11
Lapin IP, Rogawski MA (1995) Effects of D1 and D2 dopamine receptor antagonists and catecholamine depleting agents on the locomotor stimulation induced by dizocilpine in mice. Behav Brain Res 70:145–151. https://doi.org/10.1016/0166-4328(95)80004-2
Liljequist S (1991) Genetic differences in the effects of competitive and non-competitive NMDA receptor antagonists on locomotor activity in mice. Psychopharmacology 104:17–21. https://doi.org/10.1007/bf02244548
Löscher W, Hönack D (1992) The behavioural effects of MK-801 in rats: involvement of dopaminergic, serotonergic and noradrenergic systems. Eur J Pharmacol 215:199–208. https://doi.org/10.1016/0014-2999(92)90029-4
MacDonald JF, Bartlett MC, Mody I, Pahapill P, Reynolds JN, Salter MW, Schneiderman JH, Pennefather PS (1991) Actions of ketamine, phencyclidine and MK-801 on NMDA receptor currents in cultured mouse hippocampal neurones. J Physiol 432:483–508. https://doi.org/10.1113/jphysiol.1991.sp018396
Maj J, Rogóz Z, Skuza G (1991) Locomotor hyperactivity induced by MK-801 in rats. Pol J Pharmacol Pharm 43:449–458
Martin P, Svensson A, Carlsson A, Carlsson ML (1994) On the roles of dopamine D-1 vs. D-2 receptors for the hyperactivity response elicited by MK-801. J Neural Transm Gen Sect 95:113–121. https://doi.org/10.1007/bf01276430
Martin P, Waters N, Waters S, Carlsson A, Carlsson ML (1997) MK-801-induced hyperlocomotion: differential effects of M100907, SDZ PSD 958 and raclopride. Eur J Pharmacol 335:107–116. https://doi.org/10.1016/s0014-2999(97)01188-6
Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998) Rodent data and general hypothesis: antipsychotic action exerted through 5-HT2A receptor antagonism is dependent on increased serotonergic tone. J Neural Transm 105:365–396. https://doi.org/10.1007/s007020050064
McDougall SA, Moran AE, Baum TA, Apodaca MG, Real V (2017) Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose. Psychopharmacology 234:2683–2696. https://doi.org/10.1007/s00213-017-4660-3
McDougall SA, Park GI, Ramirez GI, Gomez V, Adame BC, Crawford CA (2019) Sex-dependent changes in ketamine-induced locomotor activity and ketamine pharmacokinetics in preweanling, adolescent, and adult rats. Eur Neuropsychopharmacol 29:740–755. https://doi.org/10.1016/j.euroneuro.2019.03.013
McDougall SA, Rios JW, Apodaca MG, Park GI, Montejano NR, Taylor JA, Moran AE, Robinson JAM, Baum TA, Teran A, Crawford CA (2020) Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences. Behav Brain Res 189:172857. https://doi.org/10.1016/j.bbr.2019.112302
Mele A, Fontana D, Pert A (1997) Alterations in striatal dopamine overflow during rotational behavior induced by amphetamine, phencyclidine, and MK-801. Synapse 26:218–224
Mele A, Thomas DN, Pert A (1998) Different neural mechanisms underlie dizocilpine maleate- and dopamine agonist-induced locomotor activity. Neuroscience 82:43–58. https://doi.org/10.1016/s0306-4522(97)00277-7
Mendelson SD, McEwen BS (1991) Autoradiographic analyses of the effects of restraint-induced stress on 5-HT1A, 5-HT1C and 5-HT2 receptors in the dorsal hippocampus of male and female rats. Neuroendocrinology 54:454–461. https://doi.org/10.1159/000125951
Morilak DA, Ciaranello RD (1993) Ontogeny of 5-hydroxytryptamine2 receptor immunoreactivity in the developing rat brain. Neuroscience 55:869–880. https://doi.org/10.1016/0306-4522(93)90447-n
Morilak DA, Somogyi P, Lujan-Miras R, Ciaranello RD (1994) Neurons expressing 5-HT2 receptors in the rat brain: neurochemical identification of cell types by immunocytochemistry. Neuropsychopharmacology 11:157–166. https://doi.org/10.1038/sj.npp.1380102
Nabeshima T, Yamaguchi K, Yamada K, Hiramatsu M, Kuwabara Y, Furukawa H, Kameyama T (1984) Sex-dependent differences in the pharmacological actions and pharmacokinetics of phencyclidine in rats. Eur J Pharmacol 97:217–227. https://doi.org/10.1016/0014-2999(84)90453-9
Narayanan S, Willins D, Dalia A, Wallace L, Uretsky N (1996) Role of dopaminergic mechanisms in the stimulatory effects of MK-801 injected into the ventral tegmental area and the nucleus accumbens. Pharmacol Biochem Behav 54:565–573. https://doi.org/10.1016/0091-3057(95)02220-1
National Research Council (2010) Guide for the care and use of laboratory animals, 8th edn. National Academies Press, Washington
Niddam R, Arbilla S, Scatton B, Dennis T, Langer SZ (1985) Amphetamine induced release of endogenous dopamine in vitro is not reduced following pretreatment with reserpine. Naunyn Schmiedeberg's Arch Pharmacol 329:123–127. https://doi.org/10.1007/bf00501200
Ouagazzal A, Nieoullon A, Amalric M (1993) Effects of dopamine D1 and D2 receptor blockade on MK-801-induced hyperlocomotion in rats. Psychopharmacology 111:427–434. https://doi.org/10.1007/bf02253532
Overton P, Clark D (1992) Iontophoretically administered drugs acting at the N-methyl-D-aspartate receptor modulate burst firing in A9 dopamine neurons in the rat. Synapse 10:131–140. https://doi.org/10.1002/syn.890100208
Parker EM, Cubeddu LX (1986) Effects of d-amphetamine and dopamine synthesis inhibitors on dopamine and acetylcholine neurotransmission in the striatum. II. Release in the presence of vesicular transmitter stores. J Pharmacol Exp Ther 237:193–203
Pesić V, Popić J, Milanović D, Loncarević-Vasiljković N, Rakić L, Kanazir S, Ruzdijić S (2010) The effect of MK-801 on motor activity and c-Fos protein expression in the brain of adolescent Wistar rats. Brain Res 1321:96–104. https://doi.org/10.1016/j.brainres.2010.01.048
Saland SK, Kabbaj M (2018) Sex differences in the pharmacokinetics of low-dose ketamine in plasma and brain of male and female rats. J Pharmacol Exp Ther 367:393–404. https://doi.org/10.1124/jpet.118.251652
Schiller L, Jähkel M, Oehler J (2006) The influence of sex and social isolation housing on pre- and postsynaptic 5-HT1A receptors. Brain Res 1103:76–87. https://doi.org/10.1016/j.brainres.2006.05.051
Shalaby IA, Spear LP (1980) Psychopharmacological effects of low and high doses of apomorphine during ontogeny. Eur J Pharmacol 67:451–459. https://doi.org/10.1016/0014-2999(80)90186-7
Shelnutt SR, Gunnell M, Owens SM (1999) Sexual dimorphism in phencyclidine in vitro metabolism and pharmacokinetics in rats. J Pharmacol Exp Ther 290:1292–1298
Smith CB (1963) Enhancement by reserpine and α-methyl dopa of the effects of d-amphetamine upon the locomotor activity of mice. J Pharmacol Exp Ther 142:343–350
Staiti AM, Morgane PJ, Galler JR, Grivetti JY, Bass DC, Mokler DJ (2011) A microdialysis study of the medial prefrontal cortex of adolescent and adult rats. Neuropharmacology 61:544–549. https://doi.org/10.1016/j.neuropharm.2011.04.005
Starr MS, Starr BS (1994) Comparison of the effects of NMDA and AMPA antagonists on the locomotor activity induced by selective D1 and D2 dopamine agonists in reserpine-treated mice. Psychopharmacology 114:469–476. https://doi.org/10.1007/bf02249338
Stolk JM, Rech RH (1967) Enhanced stimulant effects of d-amphetamine on the spontaneous locomotor activity of rats treated with reserpine. J Pharmacol Exp Ther 158:140–149
Sumner BE, Fink G (1997) The density of 5-hydoxytryptamine2A receptors in forebrain is increased at pro-oestrus in intact female rats. Neurosci Lett 234:7–10. https://doi.org/10.1016/s0304-3940(97)00651-4
Svensson A, Carlsson A, Carlsson ML (1992) Differential locomotor interactions between dopamine D1/D2 receptor agonists and the NMDA antagonist dizocilpine in monoamine-depleted mice. J Neural Transm 90:199–217. https://doi.org/10.1007/bf01250961
Svensson A, Carlsson ML, Carlsson A (1994) Glutamatergic neurons projecting to the nucleus accumbens can affect motor functions in opposite directions depending on the dopaminergic tone. Prog Neuro-Psychopharmacol Biol Psychiatry 18:1203–1218. https://doi.org/10.1016/0278-5846(94)90121-x
Thomas KL, Rose S, Jenner P, Marsden CD (1992) Acute reserpine treatment induces down regulation of D-1 dopamine receptor associated adenylyl cyclase activity in rat striatum. Biochem Pharmacol 44:83–91. https://doi.org/10.1016/0006-2952(92)90041-g
Uchihashi Y, Kuribara H, Tadokoro S (1992) Assessment of the ambulation-increasing effect of ketamine by coadministration with central-acting drugs in mice. Jpn J Pharmacol 60:25–31. https://doi.org/10.1254/jjp.60.25
Usun Y, Eybrard S, Meyer F, Louilot A (2013) Ketamine increases striatal dopamine release and hyperlocomotion in adult rats after postnatal functional blockade of the prefrontal cortex. Behav Brain Res 256:229–237. https://doi.org/10.1016/j.bbr.2013.08.017
Walker QD, Kuhn CM (2008) Cocaine increases stimulated dopamine release more in periadolescent than adult rats. Neurotoxicol Teratol 30:412–418. https://doi.org/10.1016/j.ntt.2008.04.002
Walker QD, Rooney MB, Wightman RM, Kuhn CM (2000) Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry. Neuroscience 95:1061–1070. https://doi.org/10.1016/s0306-4522(99)00500-x
Walker QD, Ray R, Kuhn CM (2006) Sex differences in neurochemical effects of dopaminergic drugs in rat striatum. Neuropsychopharmacology 31:1193–1202. https://doi.org/10.1038/sj.npp.1300915
Watanabe S, Fusa K, Takada K, Aono Y, Saigusa T, Koshikawa N, Cools AR (2005) Effects of alpha-methyl-p-tyrosine on extracellular dopamine levels in the nucleus accumbens and the dorsal striatum of freely moving rats. J Oral Sci 47:185–190. https://doi.org/10.2334/josnusd.47.185
Wilson C, Kercher M, Quinn B, Murphy A, Fiegel C, McLaurin A (2007) Effects of age and sex on ketamine-induced hyperactivity in rats. Physiol Behav 91:202–207. https://doi.org/10.1016/j.physbeh.2007.02.010
Witkin JM, Monn JA, Schoepp DD, Li X, Overshiner C, Mitchell SN, Carter G, Johnson B, Rasmussen K, Rorick-Kehn LM (2016) The rapidly acting antidepressant ketamine and the mGlu2/3 receptor antagonist LY341495 rapidly engage dopaminergic mood circuits. J Pharmacol Exp Ther 358:71–82. https://doi.org/10.1124/jpet.116.233627
Yamamoto T, Nakayama T, Yamaguchi J, Matsuzawa M, Mishina M, Ikeda K, Yamamoto H (2016) Role of the NMDA receptor GluN2D subunit in the expression of ketamine-induced behavioral sensitization and region-specific activation of neuronal nitric oxide synthase. Neurosci Lett 610:48–53. https://doi.org/10.1016/j.neulet.2015.10.049
Zilles K, Schleicher A, Glaser T, Traber J, Rath M (1985) The ontogenetic development of serotonin (5-HT1) receptors in various cortical regions of the rat brain. Anat Embryol 172:255–264. https://doi.org/10.1007/bf00318973
Zorrilla EP (1997) Multiparous species present problems (and possibilities) to developmentalists. Dev Psychobiol 30:141–150. https://doi.org/10.1002/(SICI)1098-2302(199703)30:2<141::AID-DEV5>3.0.CO;2-Q
Funding
This research was supported by NIGMS training grant GM083883.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Subjects were cared for according to the “Guide for the Care and Use of Laboratory Animals” (National Research Council 2010) under a research protocol approved by the Institutional Animal Care and Use Committee of CSUSB
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
McDougall, S.A., Apodaca, M.G., Park, G.I. et al. MK801-induced locomotor activity in preweanling and adolescent male and female rats: role of the dopamine and serotonin systems. Psychopharmacology 237, 2469–2483 (2020). https://doi.org/10.1007/s00213-020-05547-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-020-05547-3