Antagonism of stimulus properties of nicotine by dihydro-β-erythroidine (DHβE) in rats

Rationale: Previous work has shown that a dose of DH beta E, 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 DH beta E 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 DH beta E, 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 SC nicotine in a two-lever procedure maintained under a tandem VI60 -FR10 schedule of food reinforcement, the offset of antagonism by DH beta E was examined 5, 15 and 30 min following injection of nicotine (0.2 or 0.4 mg/kg SC) or vehicle. Results: Administration of DH beta E (0.5, 1.6 and 5.0 mg/kg SC) 30 min before nicotine failed to block nicotine (0.4 mg/kg) CTA, while co-administration of DH beta E (5.0 mg/kg SC) with nicotine (0.2 and 0.4 mg/kg SC) prevented the development of CTAs. This blockade complemented nicotine discrimination data in which DH beta E blocked the discriminative stimulus effect of nicotine (0.2 or 0.4 mg/kg SC) for 45 min after its administration. Conclusions: These observations of DH beta E'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.