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- W1252241257 abstract "Rationale: Reports have indicated that adminis- tration of nicotine inhibits, while withdrawal of chronically administered nicotine augments effects of serotonergic 5HT2A/2C agonists. Objective: It was our objective to de- termine whether 5HT2A/2C agonists can modulate the dis- criminativestimuluseffectsofnicotineinratsoritslocomotor activity effects in mice. Methods: Adult male Sprague- Dawley rats were trained to discriminate 0.3 mg/kg nicotine base from saline in a two-lever, fixed-ratio (FR10), food- reinforced,operant-conditioningtaskduringdaily(Monday- Friday)15-minexperimentalsessions.Aftercharacterizinga dose-responsecurvefornicotine,wetestedtheabilityofthe 5HT2A/2C agonists (+/−)-1-(2,5-dimethoxy-4-iodophenyl)- 2-aminopropane HCL (DOI; 0.18-1.0 mg/kg) and 1-(4- bromo-2,5-dimethoxyphenyl)-2-aminopropane(DOB; 0.1- 1.0 mg/kg), the 5HT2C agonist 6-chloro-2-(1-piperazinyl) pyrazine hydrochloride (MK 212; 0.1 mg/kg-1.0 mg/kg), and the 5HT1A agonist (±)-8-hydroxy-2-(di-n-propylamino) tetralinhydrobromide(8-OH-DPAT;0.01mg/kg-1.0mg/kg) tomodulatenicotine'sdiscriminative stimulus effects. After finding that DOI was able to attenuate the percentage nicotine lever responding (%NLR), we tested for it to also reverse nicotine's effects on locomotor activity in mice. Results: The 5HT2A/2C agonists—in particular DOI—dose dependently attenuated %NLR. The effects of DOI were reversed by the 5HT2A/2C antagonist ketanserin. MK 212 and 8-OH-DPAT had irregular effects among rats and only reduced %NLR to below 50% levels at doses markedly sup- pressing responding. DOI also dose dependently blocked nicotine's acute rate-lowering locomotor activity effects. Conclusions: These results indicate that activation of se- rotonin 5HT2A/2C receptors can blunt the discriminative stimulus and locomotor activity effects of nicotine and presents the possibility that activation of these receptors might also be able to attenuate other effects of nicotine." @default.
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- W1252241257 date "2005-01-01" @default.
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- W1252241257 title "Attenuation of nicotine's discriminative stimulus effects in rats and its locomotor activity effects in mice by serotonergic" @default.
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