Skip to main content
SpringerLink
Log in

Appearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studies

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

The phosphodiesterase (PDE) 5 inhibitor sildenafil has been shown to display psychotropic actions in humans and animals, and has been used for the treatment of antidepressant-associated erectile dysfunction. However, its effects on the neurobiology of depression are unknown. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) inhibition is anti-depressant in animals, and increasing cGMP with sildenafil is anxiogenic in rodents. Substantial cholinergic-nitrergic interaction exists in the brain, while sildenafil shows modulatory actions on cholinergic transmission. Depression is also associated with increased cholinergic drive. Here we report that sildenafil increases muscarinic acetylcholine receptor (mAChR) signaling in human neuroblastoma cells. We also show that fluoxetine (20 mg/kg/day × 7 days), as well as a combination of sildenafil (10 mg/kg/day × 7 days) plus the antimuscarinic atropine (1 mg/kg/day × 7 days) demonstrates significant, comparable antidepressant-like effects in the rat forced swim test (FST) and also reduces cortical β-adrenergic receptor (β-AR) density, while sildenafil or atropine alone did not. Importantly, sildenafil did not modify fluoxetine’s response. Sildenafil thus demonstrates antidepressant-like effects but only after central muscarinic receptor blockade, providing evidence for cholinergic-nitrergic interactions in the neurobiology of depression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • RC Almeida CS Felisbino MG Lopez AL Rodrigues NH Gabilan (2006) ArticleTitleEvidence for the involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of memantine in mice Behav Brain Res 168 318–322 Occurrence Handle16387371 Occurrence Handle10.1016/j.bbr.2005.11.023 Occurrence Handle1:CAS:528:DC%2BD28XhtlCltbY%3D

    Article  PubMed  CAS  Google Scholar 

  • RJ Baldessarini (2006) Drug therapy of depression and anxiety disorders LL Brunton JS Lazo KL Parker (Eds) Goodman & Gilman’s the pharmacological basis of therapeutics McGraw-Hill New York 429–459

    Google Scholar 

  • HG Bernstein A Stanarius B Baumann H Henning D Krell P Danos P Falkai B Bogerts (1998) ArticleTitleNitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics Neuroscience 83 867–875 Occurrence Handle9483570 Occurrence Handle10.1016/S0306-4522(97)00461-2 Occurrence Handle1:CAS:528:DyaK1cXmvVWnug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • J Bodenstein DP Venter CB Brink (2005) ArticleTitlePhenoxybenzamine and benextramine, but not 4-diphenylacetoxy-N-[2-chloroethyl] piperidine hydrochloride, display irreversible noncompetitive antagonism at G protein-coupled receptors J Pharmacol Exper Therapeutics 314 891–905 Occurrence Handle10.1124/jpet.105.083568 Occurrence Handle1:CAS:528:DC%2BD2MXntVSitr8%3D

    Article  CAS  Google Scholar 

  • MM Bradford (1976) ArticleTitleA rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal Biochem 72 248–254 Occurrence Handle942051 Occurrence Handle10.1016/0003-2697(76)90527-3 Occurrence Handle1:CAS:528:DyaE28XksVehtrY%3D

    Article  PubMed  CAS  Google Scholar 

  • CB Brink SL Viljoen SE de Kock DJ Stein BH Harvey (2004) ArticleTitleEffects of myo-inositol versus fluoxetine and imipramine pretreatments on serotonin 5HT2A and muscarinic acetylcholine receptors in human neuroblastoma cells Metab Brain Dis 19 51–70 Occurrence Handle15214506 Occurrence Handle10.1023/B:MEBR.0000027417.74156.5f Occurrence Handle1:CAS:528:DC%2BD2cXjvVKnt7g%3D

    Article  PubMed  CAS  Google Scholar 

  • DT Chau P Rada RA Kosloff JL Taylor BG Hoebel (2001) ArticleTitleNucleus accumbens muscarinic receptors in the control of behavioral depression: antidepressant-like effects of local M1 antagonist in the Porsolt swim test Neuroscience 104 791–798 Occurrence Handle11440810 Occurrence Handle10.1016/S0306-4522(01)00133-6 Occurrence Handle1:CAS:528:DC%2BD3MXkvVegs7k%3D

    Article  PubMed  CAS  Google Scholar 

  • W Chrapko P Jurasz MW Radomski SL Archer SC Newman G Baker N Lara JM Le Melledo (2006) ArticleTitleAlteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients Neuropsychopharmacology 31 1286–1293 Occurrence Handle16319917 Occurrence Handle1:CAS:528:DC%2BD28XkslKju7c%3D

    PubMed  CAS  Google Scholar 

  • JF Cryan A Markou I Lucki (2002) ArticleTitleAssessing antidepressant activity in rodents: recent developments and future needs Trends Pharmacol Sci 23 238–245 Occurrence Handle12008002 Occurrence Handle10.1016/S0165-6147(02)02017-5 Occurrence Handle1:CAS:528:DC%2BD38XjsVWjsbo%3D

    Article  PubMed  CAS  Google Scholar 

  • LC Daws DH Overstreet (1999) ArticleTitleOntogeny of muscarinic cholinergic supersensitivity in the Flinders Sensitive Line rat Pharmacol Biochem Behav 62 367–380 Occurrence Handle9972706 Occurrence Handle10.1016/S0091-3057(98)00174-9 Occurrence Handle1:CAS:528:DyaK1MXpsFCiuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • MJ Detke I Lucki (1995) ArticleTitleDetection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: the effects of water depth Behav Brain Res 73 43–46 Occurrence Handle10.1016/0166-4328(96)00067-8 Occurrence Handle1:CAS:528:DyaK28Xht1Cqtbs%3D

    Article  CAS  Google Scholar 

  • BD Devan D Sierra-Mercado SuffixJr M Jimenez JL Bowker KB Duffy EL Spangler DK Ingram (2004) ArticleTitlePhosphodiesterase inhibition by sildenafil citrate attenuates the learning impairment induced by blockade of cholinergic muscarinic receptors in rats Pharmacol Biochem Behav 79 691–699 Occurrence Handle15582676 Occurrence Handle10.1016/j.pbb.2004.09.019 Occurrence Handle1:CAS:528:DC%2BD2cXhtVCltbnL

    Article  PubMed  CAS  Google Scholar 

  • SC Dilsaver (1986) ArticleTitleCholinergic mechanisms in depression Brain Res 396 285–316 Occurrence Handle3535999 Occurrence Handle1:STN:280:DyaL2s%2FltVymtA%3D%3D

    PubMed  CAS  Google Scholar 

  • L Eroglu B Caglayan (1997) ArticleTitleAnxiolytic and antidepressant properties of methylene blue in animal models Pharmacol Res 36 381–385 Occurrence Handle9441729 Occurrence Handle10.1006/phrs.1997.0245 Occurrence Handle1:CAS:528:DyaK1cXlvVShsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • F Ferrari A Ottani D Giuliani (2002) ArticleTitleInfluence of sildenafil on central dopamine-mediated behaviour in male rats Life Sci 70 1501–1508 Occurrence Handle11895101 Occurrence Handle10.1016/S0024-3205(01)01515-6 Occurrence Handle1:CAS:528:DC%2BD38XhvFKns7g%3D

    Article  PubMed  CAS  Google Scholar 

  • J Fritze (1993) ArticleTitleThe adrenergic-cholinergic imbalance hypothesis of depression: a review and a perspective Rev Neurosci 4 63–93 Occurrence Handle7952383 Occurrence Handle1:STN:280:DyaK2M%2FktVWjuw%3D%3D

    PubMed  CAS  Google Scholar 

  • ML Furey WC Drevets (2006) ArticleTitleAntidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial Arch Gen Psychiatry 63 1121–1129 Occurrence Handle17015814 Occurrence Handle10.1001/archpsyc.63.10.1121 Occurrence Handle1:CAS:528:DC%2BD28XhtFKhtrzL

    Article  PubMed  CAS  Google Scholar 

  • JC Gillin J Lauriello JR Kelsoe M Rapaport S Golshan WM Kenny L Sutton (1995) ArticleTitleNo antidepressant effect of biperiden compared with placebo in depression: a double-blind 6-week clinical trial Psychiatry Res 58 99–105 Occurrence Handle8570773 Occurrence Handle10.1016/0165-1781(95)02700-7 Occurrence Handle1:CAS:528:DyaK28XislGi

    Article  PubMed  CAS  Google Scholar 

  • A Harkin TJ Connor MP Burns JP Kelly (2004) ArticleTitleNitric oxide synthase inhibitors augment the effects of serotonin re-uptake inhibitors in the forced swimming test Eur Neuropsychopharmacol 14 274–281 Occurrence Handle15163436 Occurrence Handle10.1016/j.euroneuro.2003.08.010 Occurrence Handle1:CAS:528:DC%2BD2cXktF2ktLg%3D

    Article  PubMed  CAS  Google Scholar 

  • AJ Harkin KH Bruce B Craft IA Paul (1999) ArticleTitleNitric oxide synthase inhibitors have antidepressant-like properties in mice. 1. Acute treatments are active in the forced swim test Eur J Pharmacol 372 207–213 Occurrence Handle10395013 Occurrence Handle10.1016/S0014-2999(99)00191-0 Occurrence Handle1:CAS:528:DyaK1MXjvFCitr0%3D

    Article  PubMed  CAS  Google Scholar 

  • B Harvey M Carstens J Taljaard (1990) ArticleTitleLithium modulation of cortical cyclic nucleotides: evidence for the Yin-Yang hypothesis Eur J Pharmacol 175 129–136 Occurrence Handle2155792 Occurrence Handle10.1016/0014-2999(90)90223-S Occurrence Handle1:CAS:528:DyaK3cXhtFWqtb8%3D

    Article  PubMed  CAS  Google Scholar 

  • BH Harvey T Bothma A Nel G Wegener DJ Stein (2005) ArticleTitleInvolvement of the NMDA receptor, NO-cyclic GMP and nuclear factor K-beta in an animal model of repeated trauma Hum Psychopharmacol 20 367–373 Occurrence Handle15912566 Occurrence Handle10.1002/hup.695 Occurrence Handle1:CAS:528:DC%2BD2MXpvVWiu7c%3D

    Article  PubMed  CAS  Google Scholar 

  • BH Harvey ME Carstens JJ Taljaard (1994) ArticleTitleEvidence that lithium induces a glutamatergic: nitric oxide-mediated response in rat brain Neurochem Res 19 469–474 Occurrence Handle8065503 Occurrence Handle10.1007/BF00967326 Occurrence Handle1:CAS:528:DyaK2cXjtFGltb0%3D

    Article  PubMed  CAS  Google Scholar 

  • BH Harvey LP Jonker L Brand M Heenop DJ Stein (2002) ArticleTitleNMDA receptor involvement in imipramine withdrawal-associated effects on swim stress, GABA levels and NMDA receptor binding in rat hippocampus Life Sci 71 43–54 Occurrence Handle12020747 Occurrence Handle10.1016/S0024-3205(02)01561-8 Occurrence Handle1:CAS:528:DC%2BD38XjvVSqu7g%3D

    Article  PubMed  CAS  Google Scholar 

  • BH Harvey R Retief A Korff G Wegener (2006) ArticleTitleIncreased hippocampal nitric oxide synthase activity and stress responsiveness after imipramine discontinuation: role of 5HT 2A/C-receptors Metab Brain Dis 21 211–220 Occurrence Handle16865538 Occurrence Handle10.1007/s11011-006-9018-1 Occurrence Handle1:CAS:528:DC%2BD28XhtlantbnL

    Article  PubMed  CAS  Google Scholar 

  • IL Heiberg G Wegener R Rosenberg (2002) ArticleTitleReduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats Behav Brain Res 134 479–484 Occurrence Handle12191834 Occurrence Handle10.1016/S0166-4328(02)00084-0 Occurrence Handle1:CAS:528:DC%2BD38XmtlCltrg%3D

    Article  PubMed  CAS  Google Scholar 

  • DS Janowsky MK el-Yousef JM Davis HJ Sekerke (1972) ArticleTitleA cholinergic-adrenergic hypothesis of mania and depression Lancet 2 632–635 Occurrence Handle4116781 Occurrence Handle10.1016/S0140-6736(72)93021-8 Occurrence Handle1:CAS:528:DyaE3sXisFSg

    Article  PubMed  CAS  Google Scholar 

  • D Kaufer A Friedman S Seidman H Soreq (1998) ArticleTitleAcute stress facilitates long-lasting changes in cholinergic gene expression Nature 393 373–377 Occurrence Handle9620801 Occurrence Handle10.1038/30741 Occurrence Handle1:CAS:528:DyaK1cXltlyqtrY%3D

    Article  PubMed  CAS  Google Scholar 

  • J Kukkonen P Ojala J Nasman H Hamalainen J Heikkila KE Akerman (1992) ArticleTitleMuscarinic receptor subtypes in human neuroblastoma cell lines SH-SY5Y and IMR-32 as determined by receptor binding, Ca++ mobilization and northern blotting J Pharmacol Exp Ther 263 1487–1493 Occurrence Handle1335069 Occurrence Handle1:CAS:528:DyaK3sXlt12ruw%3D%3D

    PubMed  CAS  Google Scholar 

  • M Kurt SS Bilge E Aksoz O Kukula S Celik Y Kesim (2004) ArticleTitleEffect of sildenafil on anxiety in the plus-maze test in mice Pol J Pharmacol 56 353–357 Occurrence Handle15215566 Occurrence Handle1:CAS:528:DC%2BD2cXnslWlur0%3D

    PubMed  CAS  Google Scholar 

  • HK Manji JA Quiroz J Sporn JL Payne K Denicoff A Gray CA Zarate SuffixJr DS Charney (2003) ArticleTitleEnhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression Biol Psychiatry 53 707–742 Occurrence Handle12706957 Occurrence Handle10.1016/S0006-3223(03)00117-3 Occurrence Handle1:CAS:528:DC%2BD3sXjtFWktbw%3D

    Article  PubMed  CAS  Google Scholar 

  • LR Meyerson LP Wennogle MS Abel J Coupet AS Lippa CE Rauh B Beer (1982) ArticleTitleHuman brain receptor alterations in suicide victims Pharmacol Biochem Behav 17 159–163 Occurrence Handle6289359 Occurrence Handle10.1016/0091-3057(82)90279-9 Occurrence Handle1:STN:280:DyaL3s%2FhsFCjuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • HA Milman SB Arnold (2002) ArticleTitleNeurologic, psychological, and aggressive disturbances with sildenafil Ann Pharmacother 36 1129–1134 Occurrence Handle12086542 Occurrence Handle10.1345/aph.1A402 Occurrence Handle1:CAS:528:DC%2BD38XlvVSlsLw%3D

    Article  PubMed  CAS  Google Scholar 

  • E O’Hare DT Weldon K Bettin J Cleary JR Mach SuffixJr (1997) ArticleTitleSerum anticholinergic activity and behavior following atropine sulfate administration in the rat Pharmacol Biochem Behav 56 151–154 Occurrence Handle8981623 Occurrence Handle10.1016/S0091-3057(96)00172-4 Occurrence Handle1:CAS:528:DyaK2sXisVGhtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • S Pagani D Mirtella R Mencarelli D Rodriguez M Cingolani (2005) ArticleTitlePostmortem distribution of sildenafil in histological material J Anal Toxicol 29 254–257 Occurrence Handle15975255 Occurrence Handle1:CAS:528:DC%2BD2MXktVant7c%3D

    PubMed  CAS  Google Scholar 

  • CS Patil NK Jain VP Singh SK Kulkarni (2004) ArticleTitleCholinergic-NO-cGMP mediation of sildenafil-induced antinociception Ind J Exp Biol 42 361–367 Occurrence Handle1:CAS:528:DC%2BD2cXjslyhu7c%3D

    CAS  Google Scholar 

  • IA Paul P Skolnick (2003) ArticleTitleGlutamate and depression: clinical and preclinical studies Ann N Y Acad Sci 1003 250–272 Occurrence Handle14684451 Occurrence Handle10.1196/annals.1300.016 Occurrence Handle1:CAS:528:DC%2BD2cXptlGqsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • RD Porsolt G Anton N Blavet M Jalfre (1978) ArticleTitleBehavioural despair in rats: a new model sensitive to antidepressant treatments Eur J Pharmacol 47 379–391 Occurrence Handle204499 Occurrence Handle10.1016/0014-2999(78)90118-8 Occurrence Handle1:CAS:528:DyaE1cXhvVagsr0%3D

    Article  PubMed  CAS  Google Scholar 

  • RD Porsolt G Brossard C Hautbois S Roux (2000) Models of affective illness: forced swimming and tail suspension tests in rodents SJ Enna M Williams JF Barret JW Ferkany T Kenakin RD Porsolt (Eds) Current protocols in pharmacology Wiley New York 5.8.1–5.8.9

    Google Scholar 

  • H Prast A Philippu (2001) ArticleTitleNitric oxide as modulator of neuronal function Prog Neurobiol 64 51–68 Occurrence Handle11250062 Occurrence Handle10.1016/S0301-0082(00)00044-7 Occurrence Handle1:CAS:528:DC%2BD3MXhslylurc%3D

    Article  PubMed  CAS  Google Scholar 

  • J Prickaerts WC van Staveren A Sik IM Markerink-van U Niewohner FJ van der Staay A Blokland VJ de (2002) ArticleTitleEffects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat Neuroscience 113 351–361 Occurrence Handle12127092 Occurrence Handle10.1016/S0306-4522(02)00199-9 Occurrence Handle1:CAS:528:DC%2BD38Xlt1Ohsro%3D

    Article  PubMed  CAS  Google Scholar 

  • JP Reneric M Bouvard L Stinus (2001) ArticleTitleIdazoxan and 8-OH-DPAT modify the behavioral effects induced by either NA, or 5-HT, or dual NA/5-HT reuptake inhibition in the rat forced swimming test Neuropsychopharmacology 24 379–390 Occurrence Handle11182533 Occurrence Handle10.1016/S0893-133X(00)00214-1 Occurrence Handle1:CAS:528:DC%2BD3MXht12gtbw%3D

    Article  PubMed  CAS  Google Scholar 

  • JP Reneric M Bouvard L Stinus (2002a) ArticleTitleIn the rat forced swimming test, chronic but not subacute administration of dual 5-HT/NA antidepressant treatments may produce greater effects than selective drugs Behav Brain Res 136 521–532 Occurrence Handle10.1016/S0166-4328(02)00203-6 Occurrence Handle1:CAS:528:DC%2BD38XosFCmtb8%3D

    Article  CAS  Google Scholar 

  • JP Reneric M Bouvard L Stinus (2002b) ArticleTitleIn the rat forced swimming test, NA-system mediated interactions may prevent the 5-HT properties of some subacute antidepressant treatments being expressed Eur Neuropsychopharmacol 12 159–171 Occurrence Handle10.1016/S0924-977X(02)00007-X Occurrence Handle1:CAS:528:DC%2BD38XhsFWgsLc%3D

    Article  CAS  Google Scholar 

  • VH Sethy JS Day MM Cooper (1988) ArticleTitleDose-dependent down-regulation of beta-adrenergic receptors after chronic intravenous infusion of antidepressants Prog Neuropsychopharmacol Biol Psychiatry 12 673–682 Occurrence Handle2851860 Occurrence Handle10.1016/0278-5846(88)90011-5 Occurrence Handle1:CAS:528:DyaL1cXls1egurc%3D

    Article  PubMed  CAS  Google Scholar 

  • RD Shytle AA Silver RJ Lukas MB Newman DV Sheehan PR Sanberg (2002) ArticleTitleNicotinic acetylcholine receptors as targets for antidepressants Mol Psychiatry 7 525–535 Occurrence Handle12140772 Occurrence Handle10.1038/sj.mp.4001035 Occurrence Handle1:CAS:528:DC%2BD38XlsFWrsb0%3D

    Article  PubMed  CAS  Google Scholar 

  • DM Slowiejko EL McEwen SA Ernst SK Fisher (1996) ArticleTitleMuscarinic receptor sequestration in SH-SY5Y neuroblastoma cells is inhibited when clathrin distribution is perturbed J Neurochem 66 186–196 Occurrence Handle8522952 Occurrence Handle1:CAS:528:DyaK2MXhtVSns7jN Occurrence Handle10.1046/j.1471-4159.1996.66010186.x

    Article  PubMed  CAS  Google Scholar 

  • SM Stahl (1996) Essential psychopharmacology Cambridge University Press Cambridge

    Google Scholar 

  • BE Suranyi-Cadotte TV Dam S Bodnoff R Quirion (1985) ArticleTitleVariability of chronic antidepressant treatments on beta-adrenergic receptor sites Prog Neuropsychopharmacol Biol Psychiatry 9 765–768 Occurrence Handle3003808 Occurrence Handle10.1016/0278-5846(85)90057-0 Occurrence Handle1:CAS:528:DyaL28XotF2isQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • KE Thummel DD Shen N Isoherranen HE Smith (2006) Design and optimization of dosage regimes: pharmacokinetic data LL Brunton JS Lazo KL Parker (Eds) Goodman & Gilman’s the pharmacological basis of therapeutics McGraw-Hill New York 1787–1888

    Google Scholar 

  • J Tignol PM Furlan M Gomez-Beneyto R Opsomer W Schreiber M Sweeney C Wohlhuter (2004) ArticleTitleEfficacy of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in remission from depression Int Clin Psychopharmacol 19 191–199 Occurrence Handle15201565 Occurrence Handle10.1097/01.yic.0000117902.43995.b0

    Article  PubMed  Google Scholar 

  • WC van Staveren IM Markerink-van HW Steinbusch S Behrends VJ de (2005) ArticleTitleLocalization and characterization of cGMP-immunoreactive structures in rat brain slices after NO-dependent and NO-independent stimulation of soluble guanylyl cyclase Brain Res 1036 77–89 Occurrence Handle15725404 Occurrence Handle10.1016/j.brainres.2004.12.040 Occurrence Handle1:CAS:528:DC%2BD2MXhslWkt7o%3D

    Article  PubMed  CAS  Google Scholar 

  • WC van Staveren HW Steinbusch IM Markerink-van DR Repaske MF Goy J Kotera K Omori JA Beavo VJ de (2003) ArticleTitlemRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain J Comp Neurol 467 566–580 Occurrence Handle14624489 Occurrence Handle10.1002/cne.10955 Occurrence Handle1:CAS:528:DC%2BD3sXhtVSmtbvO

    Article  PubMed  CAS  Google Scholar 

  • V Volke G Wegener E Vasar (2003) ArticleTitleAugmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice J Physiol Pharmacol 54 653–660 Occurrence Handle14726618 Occurrence Handle1:CAS:528:DC%2BD2cXnvFCmtg%3D%3D

    PubMed  CAS  Google Scholar 

  • G Wegener V Volke BH Harvey R Rosenberg (2003) ArticleTitleLocal, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity Brain Res 959 128–134 Occurrence Handle12480166 Occurrence Handle10.1016/S0006-8993(02)03738-1 Occurrence Handle1:CAS:528:DC%2BD38XptlWmtL0%3D

    Article  PubMed  CAS  Google Scholar 

  • ML Wong F Whelan P Deloukas P Whittaker M Delgado RM Cantor SM McCann J Licinio (2006) ArticleTitlePhosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response Proc Natl Acad Sci USA 103 15124–15129 Occurrence Handle17008408 Occurrence Handle10.1073/pnas.0602795103 Occurrence Handle1:CAS:528:DC%2BD28XhtFamurrM

    Article  PubMed  CAS  Google Scholar 

  • Y Xu BS Ku HY Yao YH Lin X Ma YH Zhang XJ Li (2005) ArticleTitleAntidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats Pharmacol Biochem Behav 82 200–206 Occurrence Handle16171853 Occurrence Handle10.1016/j.pbb.2005.08.009 Occurrence Handle1:CAS:528:DC%2BD2MXhtVyntL7I

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit for Drug Research and Development, Division of Pharmacology, North-West University (PUK), Potchefstroom, South Africa

    C. B. Brink, J. D. Clapton, B. E. Eagar & B. H. Harvey

Authors
  1. C. B. Brink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. D. Clapton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. E. Eagar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. H. Harvey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. B. Brink.

Additional information

Correspondence: Christiaan B. Brink, Division of Pharmacology, North-West University (PUK), Internal Box 16, Potchefstroom 2520, South Africa

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brink, C., Clapton, J., Eagar, B. et al. Appearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studies. J Neural Transm 115, 117–125 (2008). https://doi.org/10.1007/s00702-007-0806-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-007-0806-5

Search

Navigation