Modulatory actions of benzodiazepine receptor ligands on agonistic behaviour.
Several experiments were conducted to establish the role of benzodiazepine (BDZ) receptor ligands in aggressive behaviour in male and female rats. In particular, the pro-aggressive effects of BDZ agonists was subject of investigation. Predatory aggression (mouse killing) was facilitated by chlordiazepoxide (CDP) when tested in naive female rats, but CDP was unable to induce muricide in non-killing rats with extensive experience with mice. In experiments on maternal aggression in rats a post-hoc analysis revealed that the pro-aggressive action of CDP on maternal aggression was base line dependent: the increase in aggression in spontaneously low aggressive females was significantly higher than in females with a higher base line level. A further study aimed at unravelling the underlying factors contributing to this pro-aggressive action by determining the role of opponent size on the effects induced by CDP. Normally large opponents evoke less aggression from lactating females than smaller opponents and CDP exerted its pro-aggressive effect particularly strongly in the 'large opponent' situation. An ethological analysis was made of lateral display--an ambivalent posture frequently occurring in agonistic behaviour--to establish whether CDP indirectly increases aggression by reducing fear by means of its anxiolytic properties. The data partly support this hypothesis. These findings stress the importance of environmental and experiential factors in the possible outcome of CDP effects on aggression. Moreover, they point to possible explanations of seemingly contradictory data. In two final experiments an inverse benzodiazepine receptor agonist (beta-CCE) was tested in maternal aggression. beta-CCE reduced aggression, although not in a completely specific way. A neutral BDZ-receptor antagonist (Ro 15-1788) was tried in an attempt to antagonize the pro-aggressive effects of CDP in maternal aggression. Ro 15-1788 did not counteract the pro-aggressive action of CDP, but antagonized CDP effects on exploration. The modulatory role of the benzodiazepine receptor complex in aggression remains an intriguing area of research in which many subtleties in testing conditions play a role and in which more BDZ agonists, inverse agonists and antagonists have to be tested.
Mos
J
J
Duphar B.V., Department of Pharmacology, Weesp, Holland.
Olivier
B
B
van der Poel
A M
AM
D000374:Aggression / Q000187:drug effects*; D000378:Agonistic Behavior / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D008425:Maternal Behavior / Q000187:drug effects; D051379:Mice; D011235:Predatory Behavior / Q000187:drug effects; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*
D002243:Carbolines; D011963:Receptors, GABA-A; D005442:Flumazenil; D002707:Chlordiazepoxide; C024915:beta-carboline-3-carboxylic acid ethyl ester