ISSN:
1432-2072
Keywords:
Nicotine
;
Cholinergic receptors
;
nAChRs
;
Drug discrimination
;
Acute tolerance
;
Rats
;
Antagonism
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Current concepts concerning nicotine's CNS mechanism(s) of action suggest that this drug produces its effects via an interaction at nicotinic-cholinergic receptors (nAChRs) sensitive to acetylcholine. In vitro research further suggests that, following its initial agonist effect, this cholinergic drug may also induce a rapid desensitization of the nAChR similar to that of acetylcholine, resulting in termination of its pharmacological effect. Research described in this paper provides evidence of this secondary desensitization process in vivo by demonstrating nicotine's ability to induce acute tolerance in a Discriminative Stimulus (DS) paradigm. The ability of nicotine (400 µg/kg, SC) to elicit DS control of behavior in a two-lever operant procedure was significantly reduced via a challenge dose (800 µg/kg, SC) of nicotine administered 15–180 min before the training dose. Twenty-three of 52 rats demonstrated this phenomenon. The time to develop acute tolerance varied, providing additional evidence that these effects may be contingent upon individual rat variability. In addition, physostigmine was also observed to induce a similar desensitization in a random population of desensitizing rats. Lastly, there were no differences between desensitizers and non-desensitizers in relation to the ability of mecamylamine (1000 µg/kg, SC) to antagonize the DS, while in both populations of rats scopolamine (100 µg/kg, SC) failed to antagonize the DS.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02249336
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