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

Rationale: Previous work has shown that a dose of DH beta E, a competitive nicotinic receptor antagonist that blocked the discriminative stimulus prop erties of nicotine, was insufficient to block locomotor depression or opera nt rate-reducing effects of nicotine in rats. Examination of DH beta E agai nst other behavioural effects of nicotine may help in understanding its div erse actions, Objective: The present experiments examine the aversive stimu lus properties of nicotine, a function implicated in the regulation of nico tine intake. Furthermore, to characterise the duration of pharmacological b lockade produced by DH beta E, the antagonist was examined in the drug disc rimination (DD) procedure. Methods: Using the conditioned taste aversion (C TA) paradigm, male hooded rats were trained to avoid one of two distinctive ly flavoured solutions paired with nicotine (0.2 or 0.4 mg/kg) administrati on. In rats trained to discriminate 0.2 mg/kg SC nicotine in a two-lever pr ocedure maintained under a tandem VI60 "-FR10 schedule of food reinforcemen t, the offset of antagonism by DH beta E was examined 5, 15 and 30 min foll owing injection of nicotine (0.2 or 0.4 mg/kg SC) or vehicle. Results: Admi nistration 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 bet a E (5.0 mg/kg SC) with nicotine (0.2 and 0.4 mg/kg SC) prevented the devel opment 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 o bservations of DH beta E's short-lasting antagonism against the aversive an d discriminative stimulus effects of nicotine support the involvement of th e similar subtypes of nicotinic receptor in the mediation of these diverse behavioural effects.