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The 5-HT1A receptor active compounds (R)-8-OH-DPAT and (S)-UH-301 modulate auditory evoked EEG responses in rats

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Summary.

Schizophrenics commonly demonstrate abnormalities in central filtering capability following repetitive sensory stimuli. Such sensory inhibition deficits can be mirrored in rodents following administration of psycho-stimulatory drugs. In the present study, male Sprague-Dawley rats were implanted with brain surface electrodes to record auditory evoked EEG potentials in a paired-stimulus paradigm, using 87 dB clicks delivered 0.5 s apart. Amphetamine (1.83 mg/kg, i.p.) produced the expected loss of sensory inhibition, as defined by an increase in the ratio between test (T) and conditioning (C) amplitudes at N40, a mid-latency peak of the evoked potentials. Also, the 5-HT1A agonist (R)-8-OH-DPAT caused a significant increase in the TC ratio at the highest dose studied (0.5 mg/kg s.c.), while the 5-HT1A antagonist (S)-UH-301 did not significantly affect the TC ratio at any dose studied (0.1–5 mg/kg s.c.). When administered with amphetamine, a lower dose of 8-OH-DPAT (0.1 mg/kg) and the highest dose of UH-301 tested (5 mg/kg, s.c.) were able to reverse the amphetamine-induced increase in TC ratio. The findings suggest that 5-HT1A signaling is involved in sensory inhibition and support the evaluation of 5-HT1A receptor active compounds in conditions with central filtering deficits, such as schizophrenia.

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Abbreviations

8-OH-DPAT:

(R)-8-hydroxy-2-(di-n-propyl-amino)tetralin

UH-301:

(S)-5-fluoro-8-hydroxy-2-(di-n-propyl-amino)tetralin

EEG:

electro-encephalography

s.c.:

subcutaneous

i.p.:

intra-peritoneal

PPI:

pre-pulse inhibition

TC ratio:

test amplitude/condition amplitude

MANOVA:

multivariate analysis of variance

5-HT:

serotonin

DA:

dopamine

PET:

positron emission tomography

DOI:

(2,5-dimethoxy-4-iodoamphetamine

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Authors and Affiliations

  1. Medical Research, VA Medical Center, Denver, CO, U.S.A.

    K. E. Stevens

  2. Department of Psychiatry, University of Colorado Health Sciences Center at Fitzsimons, Aurora, CO, U.S.A.

    K. E. Stevens

  3. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, U.S.A.

    H. C. O’Neill

  4. Bristol Myers Squibb Company, Department of Neuroscience Biology, Pharmaceutical Research Institute, Wallingford, CT, U.S.A.

    G. M. Rose

  5. Neuroscience, Serono International S.A., Geneva, Switzerland

    J. Luthman

Authors
  1. K. E. Stevens
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  2. H. C. O’Neill
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  3. G. M. Rose
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  4. J. Luthman
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Present address: Research Area CNS & Pain Control, AstraZeneca R & D, SE-151 85 Södertälje, Sweden.

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Stevens, K., O’Neill, H., Rose, G. et al. The 5-HT1A receptor active compounds (R)-8-OH-DPAT and (S)-UH-301 modulate auditory evoked EEG responses in rats. Amino Acids 31, 365–375 (2006). https://doi.org/10.1007/s00726-006-0374-2

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  • DOI: https://doi.org/10.1007/s00726-006-0374-2

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