Antagonism of stimulus properties of nicotine by dihydro-beta-erythroidine (DHbetaE) in rats

Rationale: 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.