Antagonism of stimulus properties of nicotine by dihydro-beta-erythroidine (DHbetaE) in rats.
BACKGROUND
Previous work has shown that a dose of DHbetaE, a competitive nicotinic receptor antagonist that blocked the discriminative stimulus properties of nicotine, was insufficient to block locomotor depression or operant rate-reducing effects of nicotine in rats. Examination of DHbetaE against other behavioural effects of nicotine may help in understanding its diverse actions.


OBJECTIVE
The present experiments examine the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake. Furthermore, to characterise the duration of pharmacological blockade produced by DHbetaE, the antagonist was examined in the drug discrimination (DD) procedure.


METHODS
Using the conditioned taste aversion (CTA) paradigm, male hooded rats were trained to avoid one of two distinctively flavoured solutions paired with nicotine (0.2 or 0.4 mg/kg) administration. In rats trained to discriminate 0.2 mg/kg s.c. nicotine in a two-lever procedure maintained under a tandem V160''-FR10 schedule of food reinforcement, the offset of antagonism by DHbetaE was examined 5, 15 and 30 min following injection of nicotine (0.2 or 0.4 mg/kg s.c.) or vehicle.


RESULTS
Administration of DHbetaE (0.5, 1.6 and 5.0 mg/kg s.c.) 30 min before nicotine failed to block nicotine (0.4 mg/kg) CTA, while co-administration of DHbetaE (5.0 mg/kg s.c.) with nicotine (0.2 and 0.4 mg/kg s.c.) prevented the development of CTAs. This blockade complemented nicotine discrimination data in which DHbetaE blocked the discriminative stimulus effect of nicotine (0.2 or 0.4 mg/kg s.c.) for 45 min after its administration.


CONCLUSIONS
These observations of DHbetaE's short-lasting antagonism against the aversive and discriminative stimulus effects of nicotine support the involvement of the similar subtypes of nicotinic receptor in the mediation of these diverse behavioural effects.
Shoaib
M
M
Section of Behavioural Pharmacology, Institute of Psychiatry, DeCrespigny Park, London, UK. spjumos@iop.kcl.ac.uk
Zubaran
C
C
Stolerman
I P
IP
D000704:Analysis of Variance; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004336:Drug Antagonism; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D013649:Taste / Q000187:drug effects
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine