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Updated: May 28, 2026

Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
Published on: October 29, 2012
Glutamate transporter activation enhances nicotine antinociception and attenuates nicotine analgesic tolerance
Joseph A Schroeder1, Katrina F Quick, Paige M Landry
1Department of Psychology, Behavioral Neuroscience Program, Connecticut College, New London, Connecticut 06320, USA. jasch@conncoll.edu
Abstract:
Analgesic tolerance is partially mediated by enhanced glutamatergic transmission in the CNS. β-lactam antibiotics, through glutamate transporter subtype 1 (GLT-1) activation, reduce extracellular glutamate levels and attenuate tolerance to morphine analgesia in rats. Similar to opioids, nicotine has potent analgesic properties that are subject to tolerance. The purpose of this study was to evaluate the effects of ceftriaxone, a β-lactam antibiotic and GLT-1 activator on nicotine antinociception and its tolerance. Rats were pretreated for 5 days with ceftriaxone (200 mg/kg, intraperitoneally) before evaluating their analgesic response to nicotine (1.0 or 2.5 mg/kg, subcutaneously) for seven consecutive days using the tail-flick assay. Ceftriaxone-treated rats displayed an enhanced antinociceptive response to nicotine and unlike saline-injected controls, did not develop tolerance to nicotine's analgesic effects. These results suggest that GLT-1 transporter activation enhances and preserves nicotine antinociception and identify β-lactam antibiotics as potential complementary therapeutic agents for the treatment of chronic pain.
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