Abstract
The review begins by outlining some of the animal models of anxiety that have been used to evaluate anxiolytic activity. Whereas acute screening tests such as antagonism of chemically induced convulsions and foot shock-induced aggression in mice have proved to be useful in the selection of compounds chemically related to known anxiolytics, more sophisticated animal models of anxiety (e.g., the various conflict models) appear to be required if the essential features of human anxiety are to be simulated in the laboratory. The review summarizes our experience with such a model and also critically assesses the value of “open-field” induced stress in rats as a model of anxiety that is relatively simple but which enables the investigator to try to find biochemical correlates of anxiolytic action. Using the open-field' model, we have examined the effects of a number of anxiolytics (diazepam, clobazam, and nicotinamide, the putative endogenous ligand of benzodiazepine receptors) on behaviour and neurotransmitter function in different regions of the rat brain. Evidence is presented that anxiolytics act primarily by facilitating gamma-aminobutyric (GABA)-ergic transmission in limbic regions of the brain. The review concludes by outlining some of the mechanisms whereby both the 1,5- and 1,4-benzodiazepines may exert their effects at the cellular level. Whereas there is substantial experimental evidence suggesting that GABA-ergic activity is facilitated by the anxiolytic displacing a specific protein (GABA-modulin) from some of the GABA-receptor sites, thereby facilitating chloride transport into the neurons (hyperpolarization), the distribution of the benzodiazepine receptors on nonneuronal elements (glia) suggests that these drugs have more complex actions than is generally stated. Furthermore, the interactions between the benzodiazepines, GABA, and the enkephalins in subcortical regions of the brain suggest that the pharmacological profile of these drugs cannot be explained only in terms of a facilitation of GABA-ergic transmission.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.