Overview
Mammalian memory involves multiple brain areas and neurotransmitter systems; both at the receptor and post-receptor level (Meneses, ,). Investigations of serotonin (5-hydroxytryptamine, 5-HT) involvement in memory (Meneses, ) have been significantly enhanced by the identification, classification, and cloning of multiple receptors (Hoyer et al., , ) and studies at the post-receptor level (Raymond et al., ). Emergent investigation of 5-HT7 receptor is growing but contradictory. Hence, major current questions include (1) the paradox that 5-HT7 receptor agonists and antagonists in behavioral memory tasks are revealing promnesic and antiamnesic effects; (2) 5-HT7 and 5-HT1A receptors interaction (and other 5-HT receptors), and neural markers associated to these cognitive processes and individual differences. In this work recent data are briefly revised.
5-HT7 receptor stimulation
Freret et al. () reported that with a 2-h delay, (post-training) administration of the 5-HT7 receptor antagonist SB-269970 (3 and 10 mg/kg, sc) impaired the discrimination of the novel object; but with a 4-h delay, while control mice were not able to discriminate the novel object, mice treated with the agonist 5-carboxamidotryptamine (5-CT; displaying affinity for several receptors including 5-HT7; Hoyer et al., ) showed a significant discrimination. This promnesic effect was blocked by SB-269970, but not by WAY-100135 or GR-127935 (5-HT1A or 5-HT1B/1D receptor antagonists, respectively; Hoyer et al., ). Freret et al. () conclude that 5-HT7 receptor tonically modulates cognitive processes involved in consolidation performances in object recognition and therefore, it could be a promising target to treat memory dysfunctions (especially episodically related deficits) or pathological aging. Notably, Stahl () suggests that 5-HT7 receptor (blockade) as a novel therapeutic target for antidepressant and pro-cognitive effects. Nikiforuk et al. () also conclude that antagonism of 5-HT7 receptor may represent a useful pharmacological approach in the treatment of cognitive deficits and some negative schizophrenia symptoms. Also, Tajiri et al. () and Gasbarri and Pompili () propose that the 5-HT7 receptor is a rational target for the treatment of psychiatric disorders. Certainly, more research is necessary about 5-HT7 receptor, its functional complexity in memory formation and abnormal memory as well timing of drug administration (McGaugh, ; Monleón et al., ).
Pre-training elevation of 5-HT by the selective serotonin reuptake inhibitor (SSRI) fluoxetine had no effect by itself, but facilitated passive avoidance when combined with the 5-HT1A receptor antagonist NAD-299 and this facilitation was blocked by SB-269970 (Eriksson et al., ). Likewise Eriksson et al. () reported that a reduced activation of the 5-HT1A receptor was resulting in enhanced stimulation of the 5-HT7 receptor but 5-HT7 receptor agonists LP-44 or AS19 failed to facilitate passive avoidance performance; and according with these authors LP-44 and AS19 have low efficacy to stimulate protein phosphorylation of 5-HT7 receptor-activated signaling cascades. Notably, in the mutant mouse brain (lacking pituitary adenylate cyclase, an experimental mouse model for psychiatric disorders) 5-HT7 protein expression did not differ from wild-type mice but in primary embryonic hippocampal neurons AS-19 increased neurite length and number (Tajiri et al., ). Likewise, LP-211 and 8-OHDPAT affect neurites in embryonic cultures (Speranza et al., ). Certainly, Eriksson et al. () propose that retention (in passive avoidance) is mediated through hippocampal 5-HT1A receptor activation, while the 5-HT7 receptor appears to facilitate memory processes in a broader cortico-limbic network and not the hippocampus alone. Notably, LP-211 rescued diverse defective performances, including memory in the novelty preference task as well as the abnormal activation of PAK and cofilin (key regulators of actin cytoskeleton dynamics) and of the ribosomal protein (rp) S6, whose reduced activation in MECP2 mutant neurons is responsible for the altered protein translational control (De Filippis et al., ). De Filippis et al. () indicate that pharmacological targeting of 5-HT7 receptor improves specific behavioral and molecular manifestations and these data are a first step toward the validation of an innovative systemic treatment to disorders associated with intellectual disability.
Importantly, either AS-19 or LP-211 or the dual 5-HT1A/7 receptor agonist, 8-OHDPAT, facilitated memory consolidation in an associative memory task and increased cAMP production (Pérez-García et al., ; Meneses, ; Meneses et al., ) which were reversed by SB-269970. Certainly, an association between memory and cAMP production exists (Kandel, ; Izquierdo et al., ). It should be noted however that memory formation in an autoshaping learning (Pérez-García and Meneses, ) showed that cAMP production was decreased by 8-OHDPAT if memory was improving but the opposite occurred in absence of memory. In autoshaping task, trained animals are food-restricted (at 85% of ad-libitum), receiving one autoshaping training and are tested at 1.5 h for short-term memory (STM) and at 24 and 48 h for consolidation of long-term memory (LTM) (Meneses, ). Why 8-OHDPAT improved memory (consolidation, 48 h) and increased cAMP in cortex and hippocampus (Manuel-Apolinar and Meneses, ) or decremented (Pérez-García and Meneses, ) hippocampal cAMP production? Importantly, the new 5-HT7 receptor agonist LP-211 did not affect STM; nonetheless, at 0.5 and 1.0 mg/kg it improved LTM. The 5-HT7 receptor antagonist SB-269970 (10.0 mg/kg) alone had not effect but it reversed the LP-211 (1.0 mg/kg) LTM facilitation. The scopolamine (0.2 mg/kg) induced-decrement in CR was accompanied by significant increased cAMP production. Scopolamine-induced amnesia and increments in cAMP, are significantly but not completely reversed by LP-211 (Meneses et al., ). Hence, prefrontal cortex, cAMP production and improved memory formation seem to be associated; however, this association is complex and dependent on the basal level (e.g., prevalent expression of either of 5-HT1A or 5-HT7 receptors). For instance, the time-course (0–120 h) of autoshaped responses revealed progressive performance and mRNA 5-HT1A or 5-HT7 receptors are monotonically augmented or declined in prefrontal cortex, hippocampus and raphe nuclei, respectively (Perez-Garcia and Meneses, ). Moreover, 5-HT1A receptor is increased, whereas 5-HT7 receptor levels are decreased by aging (Saroja et al., ). Also, they showed significant correlation with the time spent in target quadrant; hence according with Saroja et al. () these are two key parameter of memory retrieval which in turn unambiguously links the serotonergic receptor system to spatial memory performance.
5-HT7 receptor blockade: cognitive demand or memory impaired
Gasbarri et al. () showed that SB-269970 improved memory, decreasing the number of errors in test phase and, thus, affecting reference memory, while no effects in working memory; postulating that 5-HT7 receptor blockade had procognitive effect, when the learning task implicated a high degree of difficulty. In addition, the 5-HT7 receptor antagonists, SB-269970 or DR 4004 alone had no effect but reversed amnesia induced by scopolamine and dizocilpine (Meneses, ). Hence, 5-HT7 receptor antagonism plays an important role under poor memory or when the learning or memory is complex.
5-HT7 blockade and promiscuous affinity
In recent time, it has become evident that 5-HT7 blockade and drugs displaying promiscuous affinity have interesting effects. For instance, lurasidone (affinity for several receptors including 5-HT7) and the selective 5-HT7 receptor antagonist, SB-656104-A improved learning and memory deficits by dizocilpine (or MK-801), in the rat passive avoidance test, and AS-19 (3 mg/kg) completely blocked the attenuating effects of lurasidone (3 mg/kg); AS-19 (1–10 mg/kg) pre-training administration had no effects (Horisawa et al., ). SB-269970 (30 but not 10 mg/kg) pre-training administration produces both anti-psychotic-like (amphetamine- or phencyclidine-induced hyperactivity tests) and pro-cognitive (novel object discrimination test) activity in preclinical animal models (Waters et al., ); these authors conclude that SB-269970 is more a potent inverse agonist than SB-258741, which might be a potential explanation for the conflicting profiles in vivo (for references see Waters et al., ). Importantly, Huang et al. () reported that 5-HT1A and 5-HT7 receptors contribute to lurasidone-induced dopamine efflux, concluding that, at least partially, 5-HT1A agonist and 5-HT7 antagonist properties may contribute to reversing schizophrenia-like effects. Chronic stress impaired performance on the extra-dimensional (ED) set-shifting stage of the frontal-dependent attentional set-shifting task and amisulpride (3 mg/kg) before testing reversed this restraint-induced cognitive inflexibility and improved ED performance of the unstressed control group (Nikiforuk and Popik, ). AS-19 (10 mg/kg) pre-training alone had no effect but abolished the pro-cognitive efficacy of amisulpride (Nikiforuk and Popik, ). Nikiforuk et al. () also reported that acute administration of SB-269970 (1 mg/kg) or amisulpride (3 mg/kg) ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats; both compounds were also effective in attenuating ketamine-evoked disruption of social interactions. In contrast, neither SB-269970 nor amisulpride affected ketamine-disrupted prepulse inhibition; ketamine is a glutamatergic antagonist (Neill et al., ). Importantly, in contrast to the negative regulatory effects of long-term activation of 5-HT7 receptors on NMDA receptor signaling (in vitro) acute activation of 5-HT7 receptors promotes NMDA receptor activity (Vasefi et al., ). Hence, these findings highlight the potential for temporally differential regulation of NMDA receptors by the 5-HT7 receptor. While some inconsistencies might be related to the opposite action exerted by 5-HT1A and 5-HT7 receptors over cAMP production (Renner et al., ; Meneses, ,); certainly, in different protocols of training/testing (memory consolidation vs. STM and LTM), various brain areas and neurotransmission systems interaction might be also implicated.
5-HT1a and 5-ht7 receptors
The functional significance of 5-HT1A and 5-HT7 receptors dimerization is has been revised (Matthys et al., ; Gellynck et al., ; Herrick-Davis, ); indicating that it differentially regulates receptor signaling and trafficking (Renner et al., ). But still we do not know the implications of this in memory formation and amnesic conditions; hence, the study of signaling associated to 5-HT7 receptor in memory formation, amnesia and forgetting might provide significant insights (Meneses, ,). For instance, while the association of 5-HT7 receptor stimulation, improved memory and increased cAMP seems to be reliable findings; certainly factors such as differential regulation of hippocampal expression as well as individual differences might be important (see Meneses, ). In addition, a biphasic and brain-region selective down-regulation of cAMP concentrations is observed supporting object recognition in the rat (Hotte et al., ). Wang et al. () have noted that while it is relatively well established that cAMP signaling is involved in the mediation of memory, the reports on its role to date are inconsistent. One hypothesis is that overactive cAMP signaling impairs working memory in the aged prefrontal cortex (PFC) or activation of the cAMP signaling in the frontal cortex is necessary for working memory; the explanations for this discrepancy may include: (i) activation of cAMP signaling within the PFC and an inverted U-shape dose-response on working memory and memory optimum range of cAMP rather than an overmuch or scanty production; (ii) the continuous and dynamic updating of cAMP levels occurs at the different time-course of memory formation; (iii) cAMP activation might be beneficial for working memory under conditions that require hippocampal–PFC interactions (Wang et al., ). Given the complexity of cAMP-dependent responses; hence studies of brain areas and individual differences remain to be reported at both behavioral and cellular levels (see Wang et al., ).
Evidence exists of individual differences regarding memory (Ballaz et al., ,; Fitzpatrick et al., ; Flagel et al., ) and forgetting (Tellez et al., ); hence, it seems reasonable to suggest that in autoshaping (or sign-tracking; see Meneses, ) the increment (Manuel-Apolinar and Meneses, ) or decrement (Pérez-García and Meneses, ) cAMP production might be involving individual differences (e.g., Meneses, ,). Notably, individual variation in the magnitude and influence of cue reactivity over behavior in humans and animals suggest that cue-reactive individuals may be at greater risk for the progression to addiction and/or relapse (Anastasio et al., ).
Also, an important implication is that 5-HT7 (and/or 5-HT1A) receptors stimulation increased or decreased cAMP production (e.g., Hoyer et al., ) and improved memory (Meneses et al., ). Likewise, evidence indicates that 5-HT7 splice variants constitutively activate adenylyl cyclase (Leopoldo et al., ). It should be crucial to confirm if memory formation, amnesia, or forgetting by themselves and/or plus drugs modify adenylyl cyclase.
Hence, (1) memory requires restricted or selective cAMP production (Pérez-García and Meneses, ; Meneses, ); (2) a major and consistent emerging finding is that 5-HT7 receptor stimulation seems to facilitate memory formation and reverse memory impairment; (3) expression of 5-HT7 (and 5-HT1A) receptors are accompanying memory; (4) the 5-HT7 antagonism alone had no effect but reversed memory deficits. Notably, a combination of neural and cognitive processes may contribute an early and specific marker of disorders associated to dysfunctional cognitive skills or memory in psychiatric disorders (Millan et al., ), including Alzheimer's disease progression (Ibanez and Parra, ).
Conclusions
Behavioral and molecular studies may be particularly insightful and timely in view of the apparently contradictory notion that either 5-HT1A or 5-HT7 receptor agonists or antagonists are useful in the treatment of learning and memory disorders. Also, the distinction about normal memory or impaired memory, timing of drug administration and individual differences are providing important insights about 5-HT1A or 5-HT7 receptors stimulation and blockade.
Conflict of interest statement
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Statements
Conflict of interest
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
1
AnastasioN. C.LiuS.MailiL.SwinfordS. E.LaneS. D.FoxR. G.et al. (2014). Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity. Transl. Psychiatry4:e369. 10.1038/tp.2013.131
2
BallazS. J.AkilH.WatsonS. J. (2007a). The 5-HT7 receptor: role in novel object discrimination and relation to novelty-seeking behavior. Neuroscience149, 192–202. 10.1016/j.neuroscience.2007.07.043
3
BallazS. J.AkilH.WatsonS. J. (2007b). Analysis of 5-HT6 and 5-HT7 receptor gene expression in rats showing differences in novelty-seeking behavior. Neuroscience147, 428–438. 10.1016/j.neuroscience.2007.04.024
4
De FilippisB.NativioP.FabbriA.RicceriL.AdrianiW.LacivitaE.et al. (2014). Pharmacological stimulation of the brain serotonin receptor 7 as a novel therapeutic approach for Rett syndrome. Neuropsychopharmacology. [Epub ahead of print]. 10.1038/npp.2014.105
5
ErikssonT. M.HolstS.StanT. L.HagerT.SjögrenB.OgrenS. Ö.et al. (2012). Ce5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors. Neuropharmacology63, 1150–60. 10.1016/j.neuropharm.2012.06.061
6
FitzpatrickC. J.GopalakrishnanS.CoganE. S.YagerL. M.MeyerP. J.LovicV.et al. (2013). Variation in the form of pavlovian conditioned approach behavior among outbred male Sprague-Dawley rats from different vendors and colonies: sign-tracking vs. goal-tracking. PLoS ONE8:e75042. 10.1371/journal.pone.0075042
7
FlagelS. B.WaselusM.ClintonS. M.WatsonS. J.AkilH. (2014). Antecedents and consequences of drug abuse in rats selectively bred for high and low response to novelty. Neuropharmacology76(pt B), 425–436. 10.1016/j.neuropharm.2013.04.033
8
FreretT.PaizanisE.BeaudetG.Gusmao-MontaigneA.NeeG.DauphinF.et al. (2014). Modulation of 5-HT7 receptor: effect on object recognition performances in mice. Psychopharmacology (Berl). 231, 393–400. 10.1007/s00213-013-3247-x
9
GasbarriA.CifarielloA.PompiliA.MenesesA. (2008). Effect of 5-HT7 antagonist SB-269970 in the modulation of working and reference memory in the rat. Behav. Brain. Res. 195, 164–170. 10.1016/j.bbr.2007.12.020
10
GasbarriA.PompiliA. (2014). Serotonergic 5-HT7 receptors and cognition. Rev. Neurosci. 25, 311–323. 10.1515/revneuro-2013-0066
11
GellynckE.HeyninckK.AndressenK. W.HaegemanG.LevyF. O.VanhoenackerP.et al. (2013). The serotonin 5-HT7 receptors: two decades of research. Exp. Brain Res. 230, 555–568. 10.1007/s00221-013-3694-y
12
Herrick-DavisK. (2013). Functional significance of serotonin receptor dimerization. Exp. Brain. Res. 230, 375–386. 10.1007/s00221-013-3622-1
13
HorisawaT.NishikawaH.TomaS.IkedaA.HoriguchiM.OnoM.et al. (2013). The role of 5-HT7 receptor antagonism in the amelioration of MK-801-induced learning and memory deficits by the novel atypical antipsychotic drug lurasidone. Behav. Brain Res. 244, 66–69. 10.1016/j.bbr.2013.01.026
14
HotteM.DauphinF.FreretT.BoulouardM.LevalletG. (2012). A biphasic and brain-region selective down-regulation of cyclic adenosine monophosphate concentrations supports object recognition in the rat. PLoS ONE7:e32244. 10.1371/journal.pone.0032244
15
HoyerD.ClarkeD. E.FozardJ. R.HartigP. R.MartinG. R.MylecharaneE. J.et al. (1994). International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol. Rev. 46, 157–203.
16
HoyerD.HannonJ. P.MartinG. R. (2002). Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol. Biochem. Behav. 71, 533–554. 10.1016/S0091-3057(01)00746-8
17
HuangM.PanosJ. J.KwonS.OyamadaY.RajagopalL.MeltzerH. Y. (2014). Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5-HT)2A and DA D2 antagonism and 5-HT1A partial agonism. J. Neurochem. 128, 938–949. 10.1111/jnc.12512
18
IbanezA.ParraM. A. (2014). Mapping memory binding onto the connectome's temporal dynamics: toward a combined biomarker for Alzheimer's disease. Front. Hum. Neurosci. 8:237. 10.3389/fnhum.2014.00237
19
IzquierdoI.BevilaquaL. R.RossatoJ. I.BoniniJ. S.MedinaJ. H.CammarotaM. (2006). Different molecular cascades in different sites of the brain control memory consolidation. Trends Neurosci. 29, 496–505. 10.1016/j.tins.2006.07.005
20
KandelE. R. (2001). The molecular biology of memory storage: a dialogue between genes and synapses. Science294, 1030–1038. 10.1126/science.1067020
21
LeopoldoM.LacivitaE.BerardiF.PerroneR.HedlundP. B. (2011). Serotonin 5-HT7 receptor agents: structure-activity relationships and potential therapeutic applications in central nervous system disorders. Pharmacol. Ther. 129, 120–148. 10.1016/j.pharmthera.2010.08.013
22
Manuel-ApolinarL.MenesesA. (2004). 8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical cAMP production. Behav. Brain Res. 148, 179–184. 10.1016/S0166-4328(03)00186-4
23
MatthysA.HaegemanG.Van CraenenbroeckK.VanhoenackerP. (2011). Role of the 5-HT7 receptor in the central nervous system: from current status to future perspectives. Mol. Neurobiol. 43, 228–253. 10.1007/s12035-011-8175-3
24
McGaughJ. L. (1989). Dissociating learning and performance: drug and hormone enhancement of memory storage. Brain Res. Bull. 23, 339–345. 10.1016/0361-9230(89)90220-7
25
MenesesA. (2003). A pharmacological analysis of an associative learning task: 5-HT(1) to 5-HT(7) receptor subtypes function on a pavlovian/instrumental autoshaped memory. Learn. Mem. 10, 363–372. 10.1101/lm.60503
26
MenesesA. (2004). Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task. Behav. Brain Res. 155, 275–282. 10.1016/j.bbr.2004.04.026
27
MenesesA. (2013) 5-HT systems: emergent targets for memory formation and memory alterations. Rev. Neurosci. 24, 629–664. 10.1515/revneuro-2013-0026
28
MenesesA. (2014a). Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative. Rev. Neurosci. 25, 325–356. 10.1515/revneuro-2014-0001
29
MenesesA. (2014b). Neurotransmitters and memory: cholinergic, glutamatergic, gabaergic, dopaminergic, serotonergic, signaling, and memory, in Identification of Neural Markers Accompanying Memory, ed MenesesA. (San Diego, CA: Elsevier), 5–45.
30
MenesesA.Perez-GarciaG.Liy-SalmeronG.LacivitaE.LeopoldoM. (2014). Effects of the 5-HT7 receptor agonist LP-211 during memory formation and amnesia. Psychopharmacology.
31
MillanM. J.AgidY.BrüneM.BullmoreE. T.CarterC. S.ClaytonN. S.et al. (2012). Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat. Rev. Drug Discov. 11, 141–168. 10.1038/nrd3628
32
MonleónS.Vinader-CaerolsC.ArenasM. C.ParraA. (2008). Antidepressant drugs and memory: insights from animal studies. Eur. Neuropsychopharmacol. 18, 235–248. 10.1016/j.euroneuro.2007.07.001
33
NeillJ. C.BarnesS.CookS.GraysonB.IdrisN. F.McLeanS. L.et al. (2010). Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. Pharmacol. Ther. 128, 419–432. 10.1016/j.pharmthera.2010.07.004
34
NikiforukA.KosT.FijałK.HołujM.RafaD.PopikP. (2013). Effects of the selective 5-HT7 receptor antagonist SB-269970 and amisulpride on ketamine-induced schizophrenia-like deficits in rats. PLoS ONE8:e66695. 10.1371/journal.pone.0066695
35
NikiforukA.PopikP. (2013). Amisulpride promotes cognitive flexibility in rats: the role of 5-HT7 receptors. Behav. Brain. Res. 248, 136–140. 10.1016/j.bbr.2013.04.008
36
Pérez-GarcíaG.Gonzalez-EspinosaC.MenesesA. (2006). An mRNA expression analysis of stimulation and blockade of 5-HT7 receptors during memory consolidation. Behav. Brain Res. 169, 83–92. 10.1016/j.bbr.2005.12.013
37
Pérez-GarcíaG.MenesesA. (2008). Ex-vivo study of 5-HT1A and 5-HT7 receptor agonists and antagonists on cAMP accumulation during memory formation and amnesia. Behav. Brain Res. 195, 139–146. 10.1016/j.bbr.2008.07.033
38
Perez-GarciaG.MenesesA. (2009). Memory time-course: mRNA 5-HT1A and 5-HT7 receptors. Behav. Brain Res. 202, 102–113. 10.1016/j.bbr.2009.03.027
39
RaymondJ. R.MukhinY. V.GelascoA.TurnerJ.CollinsworthG.GettysT. W.et al. (2001). Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacol. Ther. 92, 179–212. 10.1016/S0163-7258(01)00169-3
40
RennerU.ZeugA.WoehlerA.NiebertM.DityatevA.DityatevaG.et al. (2012). Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking. J. Cell Sci. 125, 2486–2499. 10.1242/jcs.101337
41
SarojaS. R.KimE. J.ShanmugasundaramB.HögerH.LubecG. (2014). Hippocampal monoamine receptor complex levels linked to spatial memory decline in the aging C57BL/6J. Behav. Brain Res. 264, 1–8. 10.1016/j.bbr.2014.01.042
42
SperanzaL.ChamberyA.Di DomenicoM.CrispinoM.SeverinoV.VolpicelliF.et al. (2013). The serotonin receptor 7 promotes neurite outgrowth via ERK and Cdk5 signaling pathways. Neuropharmacology67, 155–167. 10.1016/j.neuropharm.2012.10.026
43
StahlS. M. (2010). The serotonin-7 receptor as a novel therapeutic target. J. Clin. Psychiatry71, 1414-1415. 10.4088/JCP.10bs06601gry
44
TajiriM.Hayata-TakanoA.SeirikiK.OgataK.HazamaK.ShintaniN.et al. (2012). Serotonin 5-HT7 receptor blockade reverses behavioral abnormalities in PACAP-deficient mice and receptor activation promotes neurite extension in primary embryonic hippocampal neurons: therapeutic implications for psychiatric disorders. J. Mol. Neurosci. 48, 473–481. 10.1007/s12031-012-9861-y
45
TellezR.Gómez-ViquezL.Liy-SalmeronG.MenesesA. (2012). GABA, glutamate, dopamine and serotonin transporters expression on forgetting. Neurobiol. Learn. Mem. 98, 66–77. 10.1016/j.nlm.2012.05.001
46
VasefiM. S.YangK.LiJ.KrukJ. S.HeikkilaJ. J.JacksonM. F.et al. (2013). Acute 5-HT7 receptor activation increases NMDA-evoked currents and differentially alters NMDA receptor subunit phosphorylation and trafficking in hippocampal neurons. Mol. Brain6:24. 10.1186/1756-6606-6-24
47
WangZ. Z.ZhangY.LiuY. Q.ZhaoN.ZhangY. Z.YuanL.et al. (2013). RNA interference-mediated phosphodiesterase 4D splice variants knock-down in the prefrontal cortex produces antidepressant-like and cognition-enhancing effects. Br. J. Pharmacol. 168, 1001–1014. 10.1111/j.1476-5381.2012.02225.x
48
WatersK. A.SteanT. O.HammondB.VirleyD. J.UptonN.KewJ. N.et al. (2012). Effects of the selective 5-HT(7) receptor antagonist SB-269970 in animal models of psychosis and cognition. Behav. Brain Res. 228, 211–218. 10.1016/j.bbr.2011.12.009
Summary
Keywords
5-HT7 receptor, memory, dysfunctional memory, autoshaping, rats
Citation
Meneses A (2014) 5-HT7 receptor stimulation and blockade: a therapeutic paradox about memory formation and amnesia. Front. Behav. Neurosci. 8:207. doi: 10.3389/fnbeh.2014.00207
Received
16 April 2014
Accepted
22 May 2014
Published
12 June 2014
Volume
8 - 2014
Edited by
Walter Adriani, Istituto Superiore di Sanità, Italy
Reviewed by
Walter Adriani, Istituto Superiore di Sanità, Italy; Antonella Gasbarri, University of l'Aquila, Italy
Copyright
© 2014 Meneses.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: ameneses@msn.com
This article was submitted to the journal Frontiers in Behavioral Neuroscience.
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