Animal models for anxiety and response to serotonergic drugs.

In examining anxiety and the response of animal models to serotonergic drugs, four aspects should be taken into account: (1) the serotonin receptor is subdivided into at least six receptor subtypes; (2) benzodiazepines have acute anxiety-relieving effects, whereas antidepressants, serotonin-uptake inhibitors, buspirone, and serotonin antagonists have antianxiety effects only after prolonged administration; (3) diagnostic criteria differentiate several distinguishable anxiety disorders that have different responsiveness to serotonin-related drugs, and (4) various types of animal models exist, each responding differently to serotonin-related drugs. Perhaps particular animal models are relevant only for the study of one particular type of anxiety disorder. This differentiated view will be used when discussing the role of 5-hydroxytryptamine (5-HT) receptor subtypes in anxiety disorders and anxiety models. The 5-HT1A receptor is implicated in anxiety by the compounds buspirone and 8-hydroxy-2-(di-n-propyl-aminotetraline) (OHDPAT). The 5-HT1B or the 5-HT1D receptors play a role in the 'defensive burying' anxiety model and probably mediate antidepressant and antianxiety effects of serotonin-uptake inhibitors. The 5-HT1C receptor plays a role in the aversive brain stimulation anxiety model and could play a role in antianxiety effects of mianserin. The 5-HT2 receptor is selectively blocked by ritanserin. In animal 'conflict models' for anxiety, 5-HT-2-receptor antagonists are active, although they are weaker than the benzodiazepines. The 5-HT3-receptor antagonists are reported to be active in social interaction models for anxiety; however, clinical experience in anxiety using these compounds is not yet available.