Effects of a 5-HT2 receptor agonist, DOI (2,5-dimethoxy-4-iodoamphetamine), and antagonist, ketanserin, on the performance of rats on a free-operant timing schedule.
This experiment examined the effect of a 5-HT2 receptor agonist DOI (2,5-dimethoxy-4-iodoamphetamine), and antagonist, ketanserin, on temporal differentiation performance. Twelve rats were trained under the free-operant psychophysical procedure to press two levers (A and B) in 50-s trials in which sucrose reinforcement (0.6 mol/l, 50 microl) was provided intermittently for responding on A during the first half, and on B during the second half of the trial. Psychometric curves were derived from percent responding on B (%B), recorded in successive 5-s epochs of the trials; logistic functions were fitted to these data for the derivation of timing indices (T50 [time corresponding to %B=50%], epsilon [slope of the logistic curve], Weber fraction). Cumulative probability of switching in successive 5-s epochs was used to estimate the mean switching time, S50. DOI (0.0625, 0.125 and 0.25 mg/kg, s.c.) dose-dependently reduced T50 and S50. These effects of DOI (0.25 mg/kg) were antagonized by ketanserin (1.0 mg/kg). The results show that DOI alters temporal differentiation in the free-operant psychophysical procedure. The antagonistic effect of ketanserin indicates that the effect of DOI was probably mediated by 5-HT2A rather than 5-HT2C receptors, since ketanserin is relatively selective for 5-HT2A receptors. Comparison of these results with our previous findings with a 5-HT1A receptor agonist indicates that 5-HT1A and 5-HT2A receptors mediate qualitatively similar effects on temporal differentiation.
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Psychopharmacology Section, Division of Psychiatry, University of Nottingham, UK.
Kheramin
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Ho
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Miranda
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Bradshaw
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Szabadi
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D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant; D004193:Discrimination Learning; D005260:Female; D007650:Ketanserin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013998:Time Perception / Q000187:drug effects*
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine