Ja. Vivian et al., DEFEAT ENGENDERS PENTYLENETETRAZOLE-APPROPRIATE RESPONDING IN RATS - ANTAGONISM BY MIDAZOLAM, Psychopharmacology, 116(4), 1994, pp. 491-498
Defeat and the threat of defeat by an aggressive conspecific is stress
ful and may engender an anxiety- or fear-like state in animals; the pr
esent experiment investigated whether defeat generalized to the discri
minative stimulus properties of PTZ and how benzodiazepine receptors w
ere involved in this generalization. Separate groups of male Long-Evan
s rats (Rattus norvegicus) were trained to discriminate 20 mg/kg penty
lenetetrazole (PTZ) or 0.4 mg/kg midazolam (MDZ) from saline in a two-
choice drug-discrimination task. After establishing stimulus control,
PTZ- and MDZ-trained rats were exposed to an aggressive conspecific wh
ich resulted in defeat, as defined by the display of defensive and sub
missive postures as well as audible and ultrasonic vocalizations, Admi
nistration of saline after defeat resulted in greater than 80 % PTZ le
ver selection in 15 out of 25 PTZ-trained rats; this effect was attenu
ated through pretreatment with MDZ (1 mg/kg). Furthermore, short-term
defeat substitution for the PTZ discriminative stimulus was not accomp
anied by long-term changes in the post-defeat generalization curves fo
r PTZ and MDZ when compared to pre-defeat generalization curves. Nor d
id defeat alter the antagonism of PTZ by diazepam (2.5 mg/kg) or MDZ b
y flumazenil (10 mg/kg). In order further to characterize the necessar
y features for defeat substitution for the PTZ discriminative stimulus
, exposure to a threatening conspecific was also attempted by PTZ-trai
ned rats protected from physical contact with a wire mesh cage. In the
se tests, saline continued to engender greater than 50 % PTZ lever res
ponding in 15 of 25 rats. These results suggest that an anxiety-like s
tate is induced during defeat and exposure to a threatening conspecifi
c in most rats; this state, as well as the PTZ discriminative stimulus
, can be reversed by benzodiazepine receptor agonists. In contrast, sh
ort-term defeat substitution for the PTZ discriminative stimulus does
not appear to be related to long-term alterations in the benzodiazepin
e receptor.