Effect of 8-OH-DPAT on temporal discrimination following central 5-hydroxytryptamine depletion.
The 5-hydroxytryptamine (5-HT)(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) alters performance in discrete-trials timing schedules. 5-HT(1A) receptors occur both presynaptically and postsynaptically, but it is not known which receptor population mediates the effects of 8-OH-DPAT on timing. Rats received intra-raphe injections of 5,7-dihydroxytryptamine (n=16) or sham lesions (n=14). They were trained in a discrete-trials psychophysical procedure in which levers were presented at a predetermined time after the onset of each trial (2.5, 7.5,., 47.5 s). A response on lever A was reinforced if lever presentation occurred < 25 s after trial onset; a response on lever B was reinforced if lever presentation occurred >25 s after trial onset. After 70 preliminary sessions, the rats received 8-OH-DPAT (25, 50, 100, 200 microg kg(-1) sc) and saline vehicle. The percentage of responses on lever B (%B) increased as a function of time from trial onset. Under the baseline (vehicle-treatment) condition, performance did not differ between the two groups. 8-OH-DPAT did not alter the indifference point (time corresponding to %B=50%), but dose-dependently increased the Weber fraction in both groups. Forebrain concentrations of 5-HT and 5-HIAA in the lesioned group were approximately 10% of control levels. The results suggest that the effect of 8-OH-DPAT on performance on discrete-trials timing schedules is mediated by postsynaptic 5-HT(1A) receptors.
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Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Room B109, Medical School, Queen's Medical Centre, NG7 2UH, Nottingham, UK.
Chiang
T-J
TJ
Mobini
S
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Ho
M-Y
MY
Bradshaw
C M
CM
Szabadi
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D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000633:toxicity; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology; D013998:Time Perception / Q000187:drug effects*
D017661:Receptors, Presynaptic; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D004298:Dopamine; D009638:Norepinephrine