Effects of 5-HT2A receptor stimulation on the discrimination of durations by rats.
We recently found that rats' ability to discriminate durations of exteroceptive stimuli is disrupted by the non-selective 5-HT receptor agonist quipazine. Ketanserin reversed this effect, suggesting that the effect may be mediated by 5-HT2A receptors. Here, we report that the 5-HT2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) also disrupts temporal discrimination, and that this effect can be reversed by ketanserin and the highly selective 5-HT2A receptor antagonist (+/-)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL-100907). Twenty rats were trained to discriminate durations in a discrete-trials psychophysical procedure. In each 50-s trial, a light was presented for t seconds, following which two levers (A and B) were presented. A response on A was reinforced if t < 25 s, and a response on B if t > 25 s. Logistic psychometric curves were fitted to the proportional choice of B (%B) for derivation of timing indices [T50: time corresponding to %B = 50; Weber fraction: (T75-T25)/2T50, where T75 and T25 are times corresponding to %B = 75 and 25, respectively]. DOI 0.25 mg kg (subcutaneous) significantly increased the Weber fraction and tended to increase T50. Ketanserin 2 mg kg (subcutaneous) did not alter either parameter, but completely antagonized the effects of DOI. Similarly, MDL-100907 0.5 and 1 mg kg (intraperitoneal) did not affect performance, but completely antagonized the effects of DOI. The results indicate that the mixed 5-HT2A/2C receptor agonist DOI disrupts temporal discrimination via stimulation of 5-HT2A receptors.
Asgari
Karim
K
Psychopharmacology Section, Division of Psychiatry bSchool of Biomedical Sciences, University of Nottingham, UK.
Body
Stephanie
S
Bak
Victoria K
VK
Zhang
Zhong-Qi
ZQ
Rickard
Jonathan F
JF
Glennon
Jeffrey C
JC
Fone
Kevin C F
KC
Bradshaw
Christopher M
CM
Szabadi
Elemér
E
D000662:Amphetamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007650:Ketanserin / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011601:Psychophysics; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013998:Time Perception / Q000187:drug effects*
D000662:Amphetamines; D005464:Fluorobenzenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D007650:Ketanserin; C079049:volinanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine