A number of chemically distinct
anxiolytics were examined for effects on defensive behavior (foot-
shock-induced freezing) in rats. Central nervous system acting drugs which are not
anxiolytics were also studied. Animals were injected with a
drug or vehicle (IP) prior to being placed in a chamber with a grid floor through which two footshocks were delivered. Behavior was observed during the pre-
shock period (2 min) and for 4 min after the second footshock. The effects of the following drugs on the duration of footshock-induced freezing were studied:
diazepam (DZP); 2-amino-4,5-(1,2-cyclohexyl)-7 phosphonoheptonic
acid (
NPC 12626); 3-((+/-)-2-carboxypiperazine-4-yl)-propyl-l-
phosphonic acid (
CPP); [(+)-5-methyl-10-11,dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-
imine (
MK-801);
buspirone hydrochloride (BUS); DL-
amphetamine sulfate (
AMP);
haloperidol (HAL); ethyl-beta-carboline-3 carboxylate (
beta-CCE). Compounds which reduced the duration of footshock-induced freezing included DZP, BUS, and the competitive
NMDA antagonists
NPC 12626 and
CPP. The non-competitive
NMDA antagonist,
MK-801, had no effect on the response. The highest dose of
amphetamine tested also reduced footshock-induced freezing. However,
amphetamine-treated animals did not locomote or rear after footshock, suggesting fear of the environment. Animals injected with DZP,
NPC 12626,
CPP or
buspirone spent at least 1.4 of the 4 post
shock minutes locomoting.
Haloperidol had no effect on freezing at the doses tested.
beta-CCE tended to increase the duration of footshock-induced freezing.(ABSTRACT TRUNCATED AT 250 WORDS)