Combination Therapies of the Neurotransmitter-Targeting Drugs Dextromethorphan, Pyrilamine and Lorcaserin in a Rat Model of Nicotine Addiction
Abstract
Given the current epidemic of nicotine dependence, the study of interactions between
neurotransmitter receptor-targeting molecules to discover possible new forms of smoking
cessation treatment is of great importance. Previous studies have shown that the neurotransmitter
receptor-targeting drugs pyrilamine (an H1 histamine antagonist), lorcaserin (a selective
5-HT2C serotonin agonist), and dextromethorphan (an NMDA glutamate antagonist) can
be used to significantly reduce IV nicotine self-administration in rats. Given the
potential for enhanced success with smoking cessation treatment using this novel approach,
the current studies were conducted to determine how 1) dextromethorphan and pyrilamine
and 2) dextromethorphan and lorcaserin interact when administered together to reduce
nicotine self-administration in rat models. Young-adult female rats were fitted with
jugular IV catheters and trained to self-administer a nicotine infusion dose. Rats
were given varying doses of both dextromethorphan and pyrilamine or dextromethorphan
and lorcaserin before each self-administration session to test an acute dose-effect
function and drug interactions. No significant interactions were observed between
dextromethorphan and pyrilamine. Treatment with the high dose of lorcaserin showed
significant reductive interactions with the low dose of dextromethorphan compared
to saline injection. Treatment with the low dose of lorcaserin also showed significant
reductive interaction with the high dose of dextromethorphan. All three drugs were
also observed to decrease locomotor activity and food pellet self-administration in
a dose-dependent manner. These results are encouraging and suggest that a combination
therapy of dextromethorphan and lorcaserin may have potential as a novel smoking cessation
treatment, although further research is required.
Description
Honors Thesis in Biology: Basis for study to be published in "Neuroscience"
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Honors thesisDepartment
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https://hdl.handle.net/10161/8889Citation
Briggs, Scott (2014). Combination Therapies of the Neurotransmitter-Targeting Drugs Dextromethorphan, Pyrilamine
and Lorcaserin in a Rat Model of Nicotine Addiction. Honors thesis, Duke University. Retrieved from https://hdl.handle.net/10161/8889.Collections
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