SELECTIVE ANTAGONISM OF BEHAVIORAL-EFFECTS OF NICOTINE BY DIHYDRO-BETA-ERYTHROIDINE IN RATS

The influence of the nicotine antagonist dihydro-beta-erythroidine (DH beta E) was examined on various behavioural effects of nicotine in ra ts. Motor activity was recorded in photocell cages whereas discriminat ive stimulus effects were examined using two-lever drug discrimination procedures with a tandem schedule of food reinforcement (n = 8 throug hout). DH beta E (0.1-3.2 mg/kg) failed to antagonise the decreases in motor activity that nicotine (0.4-0.6 mg/kg) produced in experimental ly naive rats, whereas mecamylamine (1.5 mg/kg) completely blocked thi s effect of nicotine. DH beta E (0.1-3.2 mg/kg) antagonised the increa ses in motor activity that nicotine (0.4 mg/kg) produced in rats with extensive previous exposure to both nicotine and the photocell apparat us. In rats trained to discriminate either 0.1 or 0.4 mg/kg nicotine f rom saline, DH beta E (0.1-3.2 mg/kg) blocked the discriminative stimu lus effect of nicotine. The block of the discriminative effect could b e reversed by increasing the dose of nicotine; DH beta E (1.6 mg/kg) s hifted the dose-response curve for nicotine discrimination to the righ t by a factor of 9.4. In addition, nicotine in doses of 0.32-0.64 mg/k g decreased the overall rate of lever pressing but DH beta E (1.6 mg/k g) did not influence the dose-response curve for this effect. Thus, DH beta E potently blocked the locomotor activating and discriminative s timulus effects of nicotine at doses that did not antagonise its locom otor depressant and operant response rate-reducing effects. This selec tive blockade supports the involvement of different subtypes of nicoti nic receptor in the mediation of diverse behavioural effects. Furtherm ore, the rightward shift of the dose-response curve for nicotine discr imination suggested a competitive mode of action for DH beta E.