title: The 5-HT(1A) receptor active compounds (R)-8-OH-DPAT and (S)-UH-301 modulate auditory evoked EEG responses in rats.
abstract: 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-HT(1A) 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-HT(1A) 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-HT(1A) signaling is involved in sensory inhibition and support the evaluation of 5-HT(1A) receptor active compounds in conditions with central filtering deficits, such as schizophrenia.
authors.affiliation: Medical Research, VA Medical Center, Denver, CO, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Stevens
authors.forename: H C
authors.initials: HC
authors.lastname: O'Neill
authors.forename: G M
authors.initials: GM
authors.lastname: Rose
authors.forename: J
authors.initials: J
authors.lastname: Luthman
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000661:Amphetamine / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects*; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C064282:UH 301; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000661:Amphetamine