title: Serotonin antagonists in the five-choice serial reaction time task and their interactions with nicotine.
abstract: Much research has implicated the serotonin (5-HT) system in cognitive functioning and psychomotor stimulant abuse, but its role depends on the subtypes of 5-HT receptors involved and the nature of the behavioural task. Here we aimed to extend previous studies by examining the role of 5-HT1A and 5-HT2C receptors in attentional performance. The effects of the selective 5-HT antagonists WAY-100635 and SB-242084 were assessed alone and for interactions with nicotine in the five-choice serial reaction time task in rats. The effects of several doses of WAY-100635 were tested in combination with a fixed dose of nicotine, and then various doses of nicotine were tested in combination with SB-242084. Systemic administration of WAY-100635 and SB-242084 induced opposing effects on speed-related measures in the five-choice serial reaction time task, with antagonism at 5-HT1A receptors increasing omission errors and response latency, and antagonism at 5-HT2C receptors reducing both omissions and latency, and also increasing anticipatory responses; neither drug affected accuracy. Nicotine itself improved all main indices of attention, and there was preliminary evidence that the detrimental effects of WAY-100635 on response latency were weakened by nicotine. Conversely, treatment with SB-242084 enhanced all speed-related indices of performance to above the levels seen under the influence of nicotine alone, thus suggesting that 5-HT2C antagonists might be useful to decrease reaction times if used as an add-on therapy to treat attentional decline.
authors.affiliation: Section of Behavioural Pharmacology, Institute of Psychiatry, King's College London, De Crespigny Park, London, UK.
authors.forename: Davide
authors.initials: D
authors.lastname: Quarta
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Naylor
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Glennon
authors.forename: Ian P
authors.initials: IP
authors.lastname: Stolerman
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000819:agonists / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D018722:Nicotinic Agonists; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D009538:Nicotine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide