Extinction of conflict behaviour in rats, a model which may have predictive value for drugs active in anxiety disorders

The anxiety syndrom "panic disorder" is at the moment subject of intensive biological psychiatrical research. The syndrom consists of panic attacks (intense fear) with several somatic symptoms (dizziness, palpitations, hyperventilation). Most patients develop some degree of anticipatory anxiety (i.e. fear of having anothe'r panic attack). A number of panic disorder patients develop agoraphobic symptoms. These symptoms may be described as fear to be in a situation in which no help is present if something (e.g. a panic attack) happens to the patient. It has been described that panic anxiety is benzodiazepine resistant (Sheehan (1982), McNair and Kahn (1981)), but anti-depressants have been shown to have anti-panic properties (Klein (1967), Zitrin et al (1978)). The therapeutic efficacy seems to correlate with the reuptake inhibition of serotonin (5-hydroxytryptamine (5-HT)) (Den Boer (1988)). The· triazolobenzodiazepine alprazolam has also a beneficial effect in panic disorder (Ballenger et al (1988)). It is less known that the GABAB receptor agonist baclofen also possesses anti-panic properties (Pepplinkhuizen and Bruinvels (1978), Breslow et al. (1989)). In order to investigate the mechanism responsible for the anxiolytic effect of baclofen, an animal behavioural model has been developed in which this compound is effective. Chapter I reviews the literature on the GABA-ergic system, 5-HT system, the involvement of several neurotransmitters in anxiety, various animal models for anxiety and panic disorder. The aim of the experiments was to investigate the relationship between baclofen on one hand, and the GABAAjbenzodiazepine receptor chloride channel complex and the 5-HT system on the other hand, using extinction of conflict behaviour as a tool. The Chapters II to V describe the experiments which try to shed more light on two possible mechanisms, namely GABAA and/or 5-HT involvement, by which baclofen might mediate its effect on extinction of conflict behaviour.