Pharmacological Alterations of Anxious Behaviour in Mice Depending on Both Strain and the Behavioural Situation

A previous study comparing non-emotive mice from the strain C57BL/6/ByJ with ABP/Le mice showed ABP/Le to be more anxious in an open-field situation. In the present study, several compounds affecting anxiety were assayed on ABP/Le and C57BL/6/ByJ mice using three behavioural models of anxiety: the elevated plus-maze, the light-dark discrimination test and the free exploratory paradigm. The compounds used were the full benzodiazepine receptor agonist, chlordiazepoxide, and the antagonist, flumazenil, the GABAA antagonist, bicuculline, the full 5-HT1A agonist 8-OH-DPAT, and the mixed 5-HT1A/5-HT1B agonist, RU 24969. Results showed the effect of the compounds to be dependent on both the strain and the behavioural task. Several compounds found to be anxiolytic in ABP/Le mice had an anxiogenic effect on C57BL/6/ByJ mice. More behavioural changes were observed for ABP/Le in the elevated plus-maze, but the clearest findings for C57BL/6/ByJ mice were observed in the light-dark discrimination apparatus. These data demonstrate that anxious behaviour is a complex phenomenon which cannot be described by a single behavioural task nor by the action of a single compound

Aggression, anxiety and vocalizations in animals: GABA A and 5-HT anxiolytics

A continuing challenge for preclinical research on anxiolytic drugs is to capture the affective dimension that characterizes anxiety and aggression, either in their adaptive forms or when they become of clinical concern. Experimental protocols for the preclinical study of anxiolytic drugs typically involve the suppression of conditioned or unconditioned social and exploratory behavior (e.g., punished drinking or social interactions) and demonstrate the reversal of this behavioral suppression by drugs acting on the benzodiazepine-GABA A complex. Less frequently, aversive events engender increases in conditioned or unconditioned behavior that are reversed by anxiolytic drugs (e.g., fear-potentiated startle). More recently, putative anxiolytics which target 5-HT receptor subtypes produced effects in these traditional protocols that often are not systematic and robust. We propose ethological studies of vocal expressions in rodents and primates during social confrontations, separation from social companions, or exposure to aversive environmental events as promising sources of information on the affective features of behavior. This approach focusses on vocal and other display behavior with clear functional validity and homology. Drugs with anxiolytic effects that act on the benzodiazepine-GABA A receptor complex and on 5-HT 1A receptors systematically and potently alter specific vocalizations in rodents and primates in a pharmacologically reversible manner; the specificity of these effects on vocalizations is evident due to the effectiveness of low doses that do not compromise other physiological and behavioral processes. Antagonists at the benzodiazepine receptor reverse the effects of full agonists on vocalizations, particularly when these occur in threatening, startling and distressing contexts. With the development of antagonists at 5-HT receptor subtypes, it can be anticipated that similar receptor-specificity can be established for the effects of 5-HT anxiolytics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46351/1/213_2005_Article_BF02245590.pd