Skip to main content
Log in

The effects of dopamine agonists on prepulse inhibition in healthy men depend on baseline PPI values

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale and objectives

Dopamine (DA) agonists reliably disrupt prepulse inhibition (PPI) of the startle reflex in animals but less so in humans despite cross-species similarities in the neural regulation of PPI. This study examines whether individual variation in baseline PPI may account for the inconsistencies in DA agonist-induced PPI disruption in humans.

Methods

Baseline PPI measures were obtained from 32 healthy adult men. Subjects were subsequently tested in three sessions after ingestion of placebo or active drug in a balanced double-blind design. Seventeen subjects were given 0.05 and 0.1 mg of pergolide (a direct DA agonist) and 15 subjects were given 100 and 200 mg of amantadine (an indirect DA agonist). In each treatment group, subjects were assigned to “high” and “low” PPI subgroups based on the median split of their baseline PPI.

Results

Amantadine and pergolide disrupted PPI in high- but not in low-PPI subjects. In contrast, low-PPI subjects showed a trend towards PPI facilitation especially with pergolide.

Conclusions

Our results suggest that baseline PPI is an important determinant of the effect of DA agonists on PPI.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abduljawad KAJ, Langley RW, Bradshaw CM, Szabadi E (1998) Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man. J Psychopharmacol 12:239–245

    Article  PubMed  CAS  Google Scholar 

  • Abduljawad KAJ, Langley RW, Bradshaw CM, Szabadi E (1999) Effects of bromocriptine and haloperidol on prepulse inhibition: comparison of the acoustic startle eyeblink response and the N1/P2 auditory-evoked response in man. J Psychopharmacol 13:3–9

    Article  PubMed  CAS  Google Scholar 

  • Blumenthal TD (1996) Inhibition of the human startle response is affected by both prepulse intensity and eliciting stimulus intensity. Biol Psychol 44:85–104

    Article  PubMed  CAS  Google Scholar 

  • Blumenthal TD (1997) Prepulse inhibition decreases as startle reactivity habituates. Psychophysiology 34:446–450

    Article  PubMed  CAS  Google Scholar 

  • Bond AJ, Lader MH (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218

    Google Scholar 

  • Braff DL, Geyer MA (1990) Sensorimotor gating and schizophrenia: human and animal model studies. Arch Gen Psychiatry 47:181–188

    PubMed  CAS  Google Scholar 

  • Braff DL, Stone C, Callaway E, Geyer MA, Glick I, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15:339–343

    Article  PubMed  CAS  Google Scholar 

  • Braff DL, Grillon C, Geyer MA (1992) Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49:206–215

    PubMed  CAS  Google Scholar 

  • Braff DL, Swerdlow NR, Geyer MA (1999) Symptom correlates of prepulse inhibition deficits in male schizophrenic patients. Am J Psychiatry 156:596–602

    PubMed  CAS  Google Scholar 

  • Braff DL, Geyer MA, Swerdlow NR (2001) Human studies of prepulse inhibition of startle: normal subjects, patients groups, and pharmacological studies. Psychopharmacology 156:234–258

    Article  PubMed  CAS  Google Scholar 

  • British Medical Association and Royal Pharmaceutical Society of Great Britain (2005) British National Formulary, 49th edn. British Medical Association and Royal Pharmaceutical Society of Great Britain, London

  • Broersen LM, Feldon J, Weike I (1999) Dissociative effects of apomorphine infusions into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine-induced locomotion. Neuroscience 94:39–46

    Article  PubMed  CAS  Google Scholar 

  • Bubser M, Koch M (1994) Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions in the medial prefrontal cortex. Psychopharmacology 113:487–492

    Article  PubMed  CAS  Google Scholar 

  • Ellenbroek BA, Budde S, Cools AR (1996) Prepulse inhibition and latent inhibition: the role of dopamine in the medial prefrontal cortex. Neuroscience 75:535–542

    Article  PubMed  CAS  Google Scholar 

  • Factor SA (1999) Dopamine agonists. Med Clin North Am 83:415–443

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA, Krebs-Thompson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156:117–154

    Article  PubMed  CAS  Google Scholar 

  • Hamm AO, Weike AI, Schuoo HT (2001) The effect of neuroleptic medication on prepulse inhibition in schizophrenia patients: current status and future issues. Psychopharmacology 156:259–265

    Article  PubMed  CAS  Google Scholar 

  • Hardman JG, Limbird LE, Goodman Gilman A (2001) The pharmacological basis of therapeutics, 10th edn. McGraw-Hill, New York

    Google Scholar 

  • Hazlett EA, Buchsbaum MS, Tang CY, Fleischman MB, Wei TC, Byne W, Haznedar MM (2001) Thalamic activation during an attention-to-prepulse startle modification paradigm: a functional MRI study. Biol Psychiatry 50:281–291

    Article  PubMed  CAS  Google Scholar 

  • Heimans RL, Rand MJ, Fennesy MR (1972) Effects of amantadine on uptake and release of dopamine by a particulate fraction of rat basal ganglia. J Pharm Pharmacol 24:875–879

    PubMed  CAS  Google Scholar 

  • Hutchison KE, Swift R (1999) Effect of d-amphetamine on prepulse inhibition of the startle reflex in humans. Psychopharmacology 143:394–400

    Article  PubMed  CAS  Google Scholar 

  • Koch M, Schnitzler HU (1997) The acoustic startle response in rats—circuits mediating evocation, inhibition and potentiation. Behav Brain Res 89:35–49

    Article  PubMed  CAS  Google Scholar 

  • Kumari V, Gray JA (1999) Smoking withdrawal, nicotine dependence and prepulse inhibition of the acoustic startle reflex. Psychopharmacology 141:11–15

    Article  PubMed  CAS  Google Scholar 

  • Kumari V, Gray JA, Geyer MA, Ffytche D, Soni W, Mitterschiffthaler MT, Vythelingum GN, Simmons A, Williams SC, Sharma T (2003) Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects. Psychiatry Res 122:99–113

    Article  PubMed  Google Scholar 

  • Lacroix L, Broersen LM, Feldon J, Weiner I (2000) Effects of local infusions of dopaminergic drugs into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition amphetamine-induced activity. Behav Brain Res 107:111–121

    Article  PubMed  CAS  Google Scholar 

  • Langtry HD, Clissold SP (1990) Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease. Drugs 39:491–506

    PubMed  CAS  Google Scholar 

  • Mansbach RS, Geyer MA, Braff DL (1988) Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 94:507–514

    Article  PubMed  CAS  Google Scholar 

  • Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF (2003) Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A 100:6186–6191

    Article  PubMed  CAS  Google Scholar 

  • Nomikos GG, Iurlo M, Andersson JL, Kimura K, Svensson TH (1994) Systemic administration of amperozide, a new atypical antipsychotic drug, preferentially increases dopamine release in the rat medial prefrontal cortex. Psychopharmacology 115:147–156

    Article  PubMed  CAS  Google Scholar 

  • Norris H (1971) The action of sedation on brain-stem oculomotor systems in man. Neuropharmacology 10:181–191

    Article  PubMed  CAS  Google Scholar 

  • Schwarzkopf S, McCoy L, Smith D, Boutros N (1993) Test–retest reliability of prepulse inhibition of the acoustic startle response. Biol Psychiatry 34:896–900

    Article  PubMed  CAS  Google Scholar 

  • Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33

    PubMed  Google Scholar 

  • Spielberger CD (1983) Manual for the state-trait anxiety inventory. Consulting Psychologists Press, Palo Alto

    Google Scholar 

  • Stoof JC, Booij J, Drukarch B (1992) Amantadine as N-methyl-d-aspartic acid receptor antagonist. New possibilities for therapeutic application? Clin Neurol Neurosurg 94(Suppl):S4–S6

    Article  PubMed  Google Scholar 

  • Swerdlow NR, Caine SB, Braff DL, Geyer MA (1992) Neural substrates of sensorimotor gating of the startle reflex: preclinical findings and their implications. J Psychopharmacol 6:176–190

    Article  Google Scholar 

  • Swerdlow NR, Auerbach P, Monroe SM, Harston H, Geyer MA, Braff DL (1993) Men are more inhibited than women by weak prepulses. Biol Psychiatry 34:253–260

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Filion D, Geyer MA, Braff DL (1995) “Normal” personality correlates of sensorimotor, cognitive and visuospatial gating. Biol Psychiatry 37:286–299

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Hartman PL, Auerbach PP (1997) Changes in sensorimotor inhibition across the menstrual cycle: implications for neuropsychiatric disorders. Biol Psychiatry 4:452–460

    Article  Google Scholar 

  • Swerdlow NR, Taaid N, Oostwegel JL, Randolph E, Geyer MA (1998) Towards a cross-species pharmacology of sensorimotor gating: effects of amantadine, bromocriptine, pergolide and ropinirole on prepulse inhibition of acoustic startle in rats. Behav Pharmacol 9:389–396

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Eastvold A, Gerbranda T, Uyan KM, Hartman P, Doan Q, Auerbach P (2000) Effects of caffeine on sensorimotor gating of the startle reflex in normal control subjects: impact of caffeine intake and withdrawal. Psychopharmacology 151:368–378

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Platten A, Shoemaker J, Pitcher L, Auerbach P (2001) Effects of pergolide on sensorimotor gating of the startle reflex in rats. Psychopharmacology 158:230–240

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Eastvold A, Karban B, Ploum Y, Stephany N, Geyer MA, Cadenhead K, Auerbach PP (2002a) Dopamine agonist effects on startle and sensorimotor gating in normal male subjects: time course studies. Psychopharmacology 161:189–201

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Stephany N, Shoemaker JM, Ross L, Wasserman LC, Talledo J, Auerbach PP (2002b) Effects of amantadine and bromocriptine on startle and sensorimotor gating: parametric studies and cross-species comparisons. Psychopharmacology 164:82–92

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow NR, Stephany N, Wasserman LC, Talledo J, Shoemaker J, Auerbach PP (2003) Amphetamine effects on prepulse inhibition across-species: replication and parametric extension. Neuropsychopharmacology 28:640–650

    Article  PubMed  CAS  Google Scholar 

  • Vollenweider FX, Remensberger S, Hell D, Geyer MA (1999) Opposite effects of 3,4-methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus healthy humans. Psychopharmacology 143:365–372

    Article  PubMed  CAS  Google Scholar 

  • Weike AI, Bauer U, Hamm AO (2000) Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients. Biol Psychiatry 47:61–70

    Article  PubMed  CAS  Google Scholar 

  • Williams GV, Goldman-Rakic PS (1995) Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376:572–575

    Article  PubMed  CAS  Google Scholar 

  • Zavitsanou K, Cranney J, Richardson R (1999) Dopamine agonists in the orbital prefrontal cortex can reduce prepulse inhibition of the acoustic startle reflex in the rat. Pharmacol Biochem Behav 63:55–61

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors have no conflict of interest or any involvement, financial or otherwise, that might have biased the present work. This project was supported by University of Crete Research Funds Account (E.L.K.E. 1348). The studies reported in this original investigation comply with the current laws of Greece, where they were performed.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Panos Bitsios.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bitsios, P., Giakoumaki, S.G. & Frangou, S. The effects of dopamine agonists on prepulse inhibition in healthy men depend on baseline PPI values. Psychopharmacology 182, 144–152 (2005). https://doi.org/10.1007/s00213-005-0056-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-0056-x

Keywords

Navigation