OLANZAPINE, AN ATYPICAL ANTIPSYCHOTIC, INCREASES RATES OF PUNISHED RESPONDING IN PIGEONS

The effects of olanzapine [LY 170053; 2-methyl-4-(4-methyl-1-piperazin yl)-10H-thieno[2, 3b] [1,5]benzodiazepine), a potential atypical antip sychotic, were determined in pigeons whose keypeck responding was puni shed. These effects were compared to the anxiolytic agents chlordiazep oxide and pentobarbital, and to other antipsychotic agents. Keypeck be havior was maintained under a multiple FR30 FR30 schedule, signalled b y white and red stimulus lights, respectively. Each component of the s chedule alternated every 3 min with a 30-s timeout. During the white k eylight component, responding was maintained by food presentation. Dur ing the red keylight component, responding was maintained by food and simultaneously suppressed by electric shock presentation, with respons e rates being only about 5% of those during the white stimulus light. Olanzapine (0.01-1.0 mg/kg) increased punished responding at doses bel ow those which had an effect on unpunished responding. Clozapine (0.01 -1.0 mg/kg), ritanserin (0.1-3.0 mg/kg), and, to a lesser extent, risp eridone (0.1-1.0 mg/kg) were also effective at increasing punished res ponding. Generally, the maximum effect seen with olanzapine was equal to that seen with ritanserin, and it exceeded that seen with clozapine . However, these effects were generally less than those seen with chlo rdiazepoxide and pentobarbital. Haloperidol (0.01-0.1 mg/kg) was compl etely without effect on punished responding, while it caused decreases in unpunished behavior. These results provide further evidence that o lanzapine has a profile in behavioral tests unlike the typical antipsy chotic haloperidol. Moreover, this profile is similar to clozapine, a clinically effective antipsychotic with an atypical profile.