Anticonflict effects of 5HT(1A) agonists in pigeons are dependent on the level of response suppression.
Anxiety is a phenomenon that has many different manifestations. In order to test whether or not agents targeted to treat anxiety may have the properties necessary to treat differing types of anxiety, we have studied a 8-OH DPAT, buspirone, LY228729, chlordiazepoxide and pentobarbital on three different punished responding procedures in pigeons. Procedure one was a fairly standard multiple FR30 FR30 punished responding model where responding into he punished component was suppressed by electric shock to 7-10% of responding in the unpunished component. Procedure two was similar except that responding during the punished component was suppressed more severely to 1-3% of control, using increased levels of shock. Procedure three was a VI30 schedule as the unpunished component, with concomitant FR5 shock in a second component, and concomitant FR20 shock in the third component. 5HT(1A) agonists, 8-OH DPAT, buspirone and LY228729 produced the typical large increases in punished responding in procedure one, were substantially less effective when shock levels were increased in procedure two, and produced differential results which were likely due to the schedule in procedure three. The more traditional anxiolytics, chlordiazepoxide and pentobarbital, were consistently effective across all three punished responding procedures. These results would seem to indicate that 5HT(1A) agonists may not be as broadly efficacious as traditional anxiolytics, and that the state or severity of anxiety may be an important variable to predict efficacy for 5HT(1A) agonists.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
M.J.
MJ
Benvenga
J.D.
JD
Leander