Effects of acute and weekly episodic exposures to anatoxin-a on the motor activity of rats: comparison with nicotine.
Anatoxin-a is a naturally occurring nicotinic agonist produced by cyanobacterial blooms; exposures are likely to occur episodically when the blooms repeatedly form and dissipate. Tolerance and sensitization to nicotine's effects on the motor activity of rats can occur when administered episodically at weekly intervals. It was therefore of interest to compare the effects of anatoxin-a and nicotine when given weekly. Adult male Long Evans rats were tested daily (M-F) in a photocell device, that recorded both horizontal and vertical motor activity, during 30-min sessions. Anatoxin-a and nicotine were given s.c. once a week for 4 weeks, just prior to a test session. Anatoxin-a was given as the (+) isomer and as the racemate. Dose ranges were: (+)anatoxin-a, 0.075-0.225 mg/kg; (+/-)anatoxin-a, 0.2-0.95 mg/kg; and (-)-nicotine, 0.3-1.8 mg/kg. Each experiment also included a saline-control group. Nicotine initially decreased both horizontal activity and, to a greater extent, vertical activity. Tolerance developed to nicotine's effects with weekly administration. Both forms of anatoxin-a also initially decreased horizontal and vertical activity, and to roughly equivalent degrees. Neither form of anatoxin-a, however, induced tolerance with weekly administration. Thus, anatoxin-a and nicotine can be distinguished by their effects on motor activity with episodic treatment, suggesting different sites of action for the compounds in the nervous system.
MacPhail
R C
RC
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC 27711, USA. macphail.robert@epa.gov
Farmer
J D
JD
Jarema
K A
KA
D000818:Animals; D000087522:Cyanobacteria Toxins; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005731:Ganglionic Stimulants / Q000633:toxicity; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D013237:Stereoisomerism; D013997:Time Factors; D014326:Tropanes / Q000737:chemistry / Q000633:toxicity*
D000087522:Cyanobacteria Toxins; D005731:Ganglionic Stimulants; D018722:Nicotinic Agonists; D014326:Tropanes; D009538:Nicotine; C509783:anatoxin a