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Tolerance to anatoxin-a and nicotine on operant behavior: A search for mechanisms.
Citation:
JAREMA, K., J. D. FARMER, AND R. C. MACPHAIL. Tolerance to anatoxin-a and nicotine on operant behavior: A search for mechanisms. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
This experiment investigated the role of behavioral and pharmacological mechanisms in tolerance development.
Description:
Anatoxin-a is a cyanobacterial toxin of concern to EPA as it can contaminate water supplies and poison a wide variety of species by stimulating nicotinic receptors. Research has shown tolerance to the effects of (+)anatoxin-a and nicotine on operant behavior with weekly administration. This experiment investigated the role of behavioral and pharmacological mechanisms in tolerance development. Male Long Evans rats were trained to respond for food under a multiple schedule requiring completion of a variable number of responses (variable-ratio 30) or a response after a variable amount of time (variable-interval 60-sec). Groups (n=8) received weekly injections (s.c.) of either saline, nicotine (0.6 mg/kg) or (+/-)anatoxin-a (0.45 mg/kg) pre- and post-session for 4 weeks. Group assignments were: (1) vehicle pre- and post-session; (2) vehicle pre- and post-session for 3 weeks then nicotine or anatoxin- pre-session in week 4; (3) nicotine or anatoxin-a pre-session and vehicle post-session; (4) vehicle pre-session and nicotine or anatoxin-a post-session for 3 weeks then nicotine or anatoxin-a pre-session in week 4. Tolerance developed with weekly pre-session nicotine and, to a lesser extent, anatoxin-a. Weekly post-session nicotine or anatoxin-a had no effect on subsequent performance. Giving nicotine pre-session to rats that had received it post-session produced no greater effect than that obtained in rats having gotten it pre-session, indicating nicotine tolerance was due to a pharmacological mechanism. Giving anatoxin-a pre-session to rats that had received it post-session produced a slightly greater effect than that obtained in rats having gotten it pre-session, indicating tolerance to anatoxin-a was behavioral in nature. Finally, when cross-tolerance was tested, anatoxin-a rats showed complete tolerance to nicotine, whereas nicotine rats showed no tolerance to anatoxin-a. These results further highlight differences in the mechanisms underlying the behavioral toxicity of anatoxin-a and nicotine. This is an abstract of a proposed presentation; the information does not necessarily reflect Agency policy