Method of screening a compound for anxiolytic activity in an apolipoprotein E knockout animal

Abstract

Methods and compositions for use in treating anxiety are provided. In the subject methods, an effective amount of an agent having ApoE3 activity is administered to a host suffering from an anxiety, e.g. excessive anxiety, unwanted anxiety, an anxiety disorder, etc. Also provided are methods and compositions for modulating adrenal steroidogenesis and/or release, particularly stress induced adrenal steroidogenesis and/or release, and the hippocampal-pituitary-adrenal (HPA) axis. In these methods, an effective amount of an ApoE activity modulating agent, e.g. an ApoE agonist or antagonist, is administered to the host.

1 . A method of treating a mammalian host suffering from anxiety, said method comprising: 
 administering to said host an effective amount of an ApoE agonist,    whereby anxiety in said host is at least reduced.    
   
   
       2 . The method according to  claim 1 , wherein said ApoE agonist is an ApoE3 agonist.  
   
   
       3 . The method according to  claim 1 , wherein said ApoE agonist is an ApoE small molecule mimetic.  
   
   
       4 . The method according to  claim 1 , wherein said ApoE agonist is nucleic acid.  
   
   
       5 . The method according to  claim 1 , wherein said ApoE agonist is protein or analogue thereof.  
   
   
       6 . A method of screening a compound for anxiolytic activity, said method comprising: 
 (a) administering said compound to an ApoE knockout animal model;    (b) observing the effect of said compound on said animal model; and    (c) relating the observed effect of said compound on said animal model to the anxiolytic activity of said compound.    
   
   
       7 . The method according to  claim 6 , wherein said ApoE knockout animal model is a mammal.  
   
   
       8 . The method according to  claim 7 , wherein said mammal is a mouse.  
   
   
       9 . The method according to  claim 6 , wherein said ApoE knockout animal model is an ApoE3 knockout animal model.  
   
   
       10 . The method according to  claim 6 , wherein said animal model is a male.  
   
   
       11 . A method for modulating adrenal steroidogenesis and/or release in a host, said method comprising: 
 administering to said host an effective amount of an ApoE activity modulating agent;    whereby adrenal steroidogenesis and/or release is modulated in said host.    
   
   
       12 . The method according to  claim 11 , wherein said ApoE activity modulating agent is an ApoE agonist.  
   
   
       13 . The method according to  claim 12 , wherein said ApoE activity modulating agent is an ApoE antagonist.  
   
   
       14 . The method according to  claim 11 , wherein said host is a mammalian host.  
   
   
       15 . A method for modulating the HPA axis of a mammalian host, said method comprising: 
 administering to said host an effective amount of an ApoE activity modulating agent;    whereby the HPA axis of said mammalian host is modulated.    
   
   
       16 . The method according to  claim 15 , wherein said ApoE activity modulating agent is an ApoE agonist.  
   
   
       17 . The method according to  claim 15 , wherein said ApoE activity modulating agent is an ApoE antagonist.  
   
   
       18 . The method according to  claim 15 , wherein said ApoE activity modulating agent is an ApoE3 activity modulating agent.  
   
   
       19 . The method according to  claim 15 , wherein said method comprises modulating adrenal steroidogenesis and/or release in said host.  
   
   
       20 . The method according to  claim 19 , wherein said modulating modulates adrenal corticosterone production and/or release in said host.