Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo.
Snake neurotoxins (NTX) have proven to be valuable tools for the characterisation of muscular nicotinic acetylcholine receptor structure and function. It is very likely that they could also be utilised to identify subtypes of neuronal nicotinic receptors controlling specific functions within the central nervous system. In this study we examined the effects of long alpha NTX (alpha-bungarotoxin, alpha-Bgt, and alpha-cobratoxin, alpha-Cbt) and short alpha NTX (alpha-erabutoxin a, alpha-Ebt) as well as the anticholinesterase toxin fasciculin-2 (FAS), on the nicotine-evoked release of dopamine (DA) in the striatum, using the in vivo push-pull technique. The short toxins alpha-Ebt and FAS blocked the extracellular increase of DA evoked by nicotine at 4.2 microM concentrations and alpha-Ebt was more potent, as reflected by the blockade at the lower dose of 0.42 microM. In contrast, the long toxins showed a different profile of action. Alpha-Cbt did not show any blockade of the nicotine-evoked release of DA at the doses studied while alpha-Bgt did block it only at the higher dose (4.2 microM) These results indicate that short neurotoxins show a stronger interaction with striatal nicotinic receptors subtypes controlling DA release when compared to the long ones. This interaction of short neurotoxin polypeptides and presynaptic receptors may permit the further elucidation of the particular nicotinic receptor populations responsible for the modulation of striatal DA release.
Dajas-Bailador
F
F
Neurochemistry Division, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. bspfadb@bath.ac.uk
Costa
G
G
Dajas
F
F
Emmett
S
S
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D003039:Cobra Neurotoxin Proteins / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology; D004870:Erabutoxins / Q000494:pharmacology; D008297:Male; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012911:Snakes / Q000378:metabolism*
D002038:Bungarotoxins; D003039:Cobra Neurotoxin Proteins; D004546:Elapid Venoms; D009498:Neurotoxins; C038908:erabutoxin A; D004870:Erabutoxins; C025154:alpha-cobratoxin; D009538:Nicotine; C044937:fasciculin; D004298:Dopamine